Bacopa monnieri (100)

• Bacopa monnieri (1-50)

51. Mishra et al. 2016. Studies on metals and pesticide content in some Ayurvedic formulations containing Bacopa monnieri L.
52. Verma et al. 2014. Neuromodulatory role of Bacopa monnieri on oxidative stress induced by postnatal exposure to decabromodiphenyl ether (PBDE -209) in neonate and young female mice
53. Kumar & Mondal 2016. Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS Induced Model of Depression in Rat
54. Nuengchamnong, Sookying & Ingkaninan 2016. LC-ESI-QTOF-MS based screening and identification of isomeric jujubogenin and pseudojujubogenin aglycones in Bacopa monnieri extract
55. Sireeratawong et al. 2016. Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats
56. Gupta et al. 2017. Microbial modulation of bacoside A biosynthetic pathway and systemic defense mechanism in Bacopa monnieri under Meloidogyne incognita stress
57. Suganya et al. 2018. Phytofabrication of silver nanoparticles using Bacopa monnieri leaf extract and its antibacterial activity as well as oxidative stress-induced apoptosis of lung cancer
58. Kashyap, Kapoor & Kale 2015. Effect of vermicompost extracts on the in vitro micropropagation of Bacopa monnieri
59. Largia et al. 2016. Analysis of propagation of Bacopa monnieri (L.) from hairy roots, elicitation and Bacoside A contents of Ri transformed plants
60. Dethe, Deepak & Agarwal 2016. Elucidation of Molecular Mechanism(s) of Cognition Enhancing Activity of Bacomind®: A Standardized Extract of Bacopa Monnieri
61. Naik et al. 2014. Rapid one step protocol for in vitro regeneration of Bacopa monnieri (L.)
62. Jasim et al. 2016. Surfactin, Iturin, and Fengycin Biosynthesis by Endophytic Bacillus sp. from Bacopa monnieri
63. Yadav et al. 2014a. Strain specific Agrobacterium-mediated genetic transformation of Bacopa monnieri
64. Bansal, Kumar & Reddy 2015. Production of bacoside A, a memory enhancer from hairy root cultures of Bacopa monnieri (L.) Wettst
65. Katoch, Salgotra & Singh 2014. Endophytic fungi found in association with Bacopa monnieri as potential producers of industrial enzymes and antimicrobial bioactive compounds
66. Singh et al. 2016. Comparative evaluation of extract of Bacopa monnieri and Mucuna pruriens as neuroprotectant in MPTP model of Parkinson's disease
67. Roshni, Gangaprasad & Siril 2014. Evaluation of variability in Bacopa monnieri (L.) Pennell using morphological and biochemical markers
68. Ramasamy, Kiew & Chung 2014. Inhibition of Human Cytochrome P450 Enzymes by Bacopa monnieri Standardized Extract and Constituents
69. Le et al. 2015. Protective effects of Bacopa monnieri on ischemia-induced cognitive deficits in mice: The possible contribution of bacopaside I and underlying mechanism
70. Khilwani et al. 2016. Direct somatic embryogenesis and encapsulation of somatic embryos for in vitro conservation of Bacopa monnieri (L.) Wettst
71. Pei et al. 2016. Differential Inhibition of Water and Ion Channel Activities of Mammalian Aquaporin-1 by Two Structurally Related Bacopaside Compounds Derived from the Medicinal Plant Bacopa monnieri
72. Thakur et al. 2015. Bioactive isochromenone isolated from Aspergillus fumigatus, endophytic fungus from Bacopa monnieri
73. Bansal, Reddy & Kumar 2016. Seasonal variations in harvest index and bacoside A contents amongst accessions of Bacopa monnieri (L.) Wettst. collected from wild populations
74. Karataş, Aasim & Dazkirli 2016. Influence of light-emitting diodes and benzylaminopurin on adventitious shoot regeneration of water hyssop (Bacopa monnieri (L.) Pennell) in vitro
75. Dogan et al. 2015. Determination of cadmium accumulation capabilities of aquatic macrophytes Ceratophyllum demersum, Bacopa monnieri and Rotala rotundifolia
76. Taznin, Mukti & Rahmatullah 2015. Bacopa monnieri: An evaluation of antihyperglycemic and antinociceptive potential of methanolic extract of whole plants
77. Sharma et al. 2015a. Bacoside biosynthesis during in vitro shoot multiplication in Bacopa monnieri (L.) Wettst. grown in Growtek and air lift bioreactor.
78. Packyanathan, Gayathri & Vishnupriya 2016. Preliminary phytochemical analysis and cytotoxicity potential of Bacopa monnieri on oral cancer cell lines
79. Shinomol, Bharath & Muralidhara 2012. Pretreatment with Bacopa monnieri extract offsets 3-nitropropionic acid induced mitochondrial oxidative stress and dysfunctions in the striatum of prepubertal mouse brain
80. Mahender et al. 2012. A rapid and efficient method for in vitro shoot organogenesis and production of transgenic Bacopa monnieri L. mediated by Agrobacterium tumefaciens
81. Siddique et al. 2014. The effect of Bacopa monnieri leaf extract on dietary supplementation in transgenic Drosophila model of Parkinson's disease
82. Hussain & Salim 2012. Bioaccumulation Pattern of Mercury in Bacopa monnieri (L.) Pennell
83. Kumar et al. 2016. Efficacy of Standardized Extract of Bacopa monnieri (Bacognize®) on Cognitive Functions of Medical Students: A Six-Week, Randomized Placebo-Controlled Trial
84. Subramanian et al. 2014. Role of Bacopa monnieri in the temporal regulation of oxidative stress in clock mutant (cry^b) of Drosophila melanogaster
85. Krishna, Gayathri & Priya 2016. Genotoxicity potential of Bacopa monnieri on oral cancer cell lines by DNA fragmentation
86. Bin Emran et al. 2015. Molecular docking and inhibition studies on the interactions of Bacopa monnieri's potent phytochemicals against pathogenic Staphylococcus aureus
87. Kongkeaw et al. 2014. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract
88. Karataş & Aasim 2014. Efficient In Vitro Regeneration of Medicinal Aquatic Plant Water Hyssop (Bacopa monnieri L. Pennell)
89. Largia et al. 2015. Methyl jasmonate and salicylic acid synergism enhances bacoside A content in shoot cultures of Bacopa monnieri (L.)
90. Singh et al. 2015. In vitro effects of standardized extract of Bacopa monniera and its five individual active constituents on human P-glycoprotein activity
91. Shahid et al. 2016. Beneficial effects of Bacopa monnieri extract on opioid induced toxicity
92. Hussain et al. 2011. Heavy metal accumulation potential and medicinal property of Bacopa monnieri: A paradox
93. Pandey et al. 2015. Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice
94. Łojewski et al. 2014. Development of Optimal Medium Content for Bioelements Accumulation in Bacopa monnieri (L.) In Vitro Culture
95. De, Chandra & Misra 2009. Assessment of the effect of Bacopa monnieri (L.) Wettst. extract on the labeling of blood elements with technetium-99m and on the morphology of red blood cells
96. Ribeiro, Tiberio & Oliveira 2015. The effect of competition on Bacopa monnieri zonation in an temporarily open/closed tropical estuary
97. Wangdi & Sarethy 2016. Evaluation of Micropropagation System of Bacopa monnieri L. in Liquid Culture and Its Effect on Antioxidant Properties
98. Priyanka et al. 2013. Diverse age-related effects of Bacopa monnieri and donepezil in vitro on cytokine production, antioxidant enzyme activities, and intracellular targets in splenocytes of F344 male rats
99. Parveen et al. 2016. Phytochemical analysis and in vitro biological characterization of aqueous and methanolic extract of Bacopa monnieri
100. Sharma et al. 2015b. Enhanced bacoside production in shoot cultures of Bacopa monnieri under the influence of abiotic elicitors

Mishra, Amrita; Arun K. Mishra, Om Prakash Tiwari and Shivesh Jha 2016. Studies on metals and pesticide content in some Ayurvedic formulations containing Bacopa monnieri L.. Journal of Integrative Medicine 14(1): 44-50. DOI: 10.1016/S2095-4964(16)60241-8

Ayurvedic formulations, used singularly or in combination, generally contain many complex components. Quality, safety, efficacy and batch-to-batch consitency of Ayurvedic formulations are essential to meet the criteria needed to support its use worldwide. Some advantages of the Ayurvedic system over all allopathic system of medicine, are that it has fewer side effects, lower cost and generally easy availability of raw materials for formulations. (Mishra et al. 2016: 45)

I should say so. Local esoteric shops sell Ayurvedic plant powders at a reasonable price.

Environmental pollution has increasingly attracted global interest, since the beginning of this century. In fact, contamination of soils with heavy metals has become one of the challenges to be faced by several Ayurvedic manufacturers. Heavy metals are naturally present in agricultural soils at low levels. Imbalances in the concentrations of heavy metals in the soils can exert toxic effect not only on medicinal plants but also on human health. (Mishra et al. 2016: 45)

No joke. Wikipedia says 21% of Ayurvedic producs sold overall are contaminated, making their consumption a kind of a Russian roulette.

Medicinal plants that have elevated levels of heavy metals may affect the central nervous system, liver, lungs, heart, kidneys, and brain, and produce serious health hazards. Therefore, it is essential to monitor contaminants in Ayurvedic products. If these medicinal plants are incorporated in Ayurvedic formulae, these products, intended for healing, may pose high risk of heavy metal toxicity. (Mishra et al. 2016: 45)

Tragic irony. It's the medicine that kills.

Therefore, in the present investigation, trials have been made to quantify the level of nonessential, toxic heavy metals (Pb, Cd, Cr and Ni) as well as organochlorine pesticide residue in the following three Ayurvedic formulations containing Bacopa monnieri: Brahmi Ghita (BG), Brahmi Vati (BV) and Saraswat Churna (SC). BG is used to treat memory problems, insanity, epilepsy, psychiatric disorders and infertility. BV is used to improve memory, and to treat stress, anxiety, convulsions, hysteria, insomnia and epilepsy. SC is used to treat mania, epilepsy, mental weakness and nervous strain and for improving grasping power. (Mishra et al. 2016: 45)

These should be taken as "baseline" when dealing with the lengthy lists of positive effects.

All Bacopa monnieri samples contained Pb, Cd, Cr and Ni. For BG, BV and SC, the levels of Pb and Cd were within permissible limit as set by the WHO. (Mishra et al. 2016: 46)

How up-to-date is the World Health Organization on this? What about the other heavy metals?

The formulation BG, is used for memory enhancement, cardiotonic, antiepileptic and antipyretic purposes. The concentrations of Pb and Cd in BG formulation, within permissible range, indicated its safe use, however Cd levels was close to the WHo permissible limit (0.3 μg/g). WHO has set permissible limits of Pb (10 μg/g) and the limit of detection in this study was far below that threshold. (Mishra et al. 2016: 47)

So, like another toxicological study affirmed, "adverse health effects are not likely to occur" (Jain et al. 2017: 218).

High concentrations of heavy metals (more than the prescribed limits, i.e., Cr at 2 μg/g and Ni at 1.63 μg/g) cause nerve damage, fatigue and allergic dermatitis known as Nickel itch. [...] Two samples of BG (BG1 and BG3) and all four samples of BV showed higher concentration of Cr than the WHO recommendations. In each test samples, Ni concentration was higher than prescribed limit. (Mishra et al. 2016: 47)

Uh-oh.

Verma, Priya; Poonam Singh and Behrose S. Gandhi 2014. Neuromodulatory role of Bacopa monnieri on oxidative stress induced by postnatal exposure to decabromodiphenyl ether (PBDE -209) in neonate and young female mice. Iranian Journal of Basic Medical Sciences 17(4): 307-311. DOI: 10.22038/ijbms.2014.2590

Bacopa monnieri (BM), a nootropic plant belongs to Scrophulariaceae family, is found in wet, damp and marshy areas of tropical regions. B. monnieri is an important constituent of "Ayurveda" and has been mentioned in Çaraka Samhita, Suśruta-Samhita and other treatise. The presence of active saponins like bacosides A and B in BM act as antioxidant and memory enhancer. (Verma et al. 2014: 307)

The adjective "nootropic" is rather new, isn't it? Alternative: "Medhya Rasayana".

Being a highly brominated congener of polybrominated diphenyl ether, 2,2',3,3',4,4',5,5',6,6'-decabrominated diphenyl ether (PBDE-209) is used as flame retardant in wide variety of everyday products, from polyurethane foam in furniture to high-impact plastics used in computer casings. Due to its lipophilicity, PBDE-209 bioaccumulates easily in body organs and breast milk, affecting human health including developmental and neurological functions. Hence, concerns have been raised about the potential adverse health effects of PBDE-209, especially in the area of developmental neurotoxicity. (Verma et al. 2014: 307)

They don't kid around when they say some plastics as extremely poisonous.

Supplementation with graded doses of BM in PBDE-209-exposed mice showed that only the maximum dose (120 mg/kg) was significantly effective in restoring the increased levels of MDA [malondiadehide] and PC [protein carbonyl] in the FC and Hc of neonate mice (P<0.05). (Verma et al. 2014: 308)

The rule of "the more the merrier" still applies.

BM has also reported to reverse scopolamine-induced acquisition and retrieval of memory in Morris water maze task. It also repairs the damaged neurons by enhancing kinase activity and neuronal synthesis coupled with restoration of synaptic activity, thereby improving the nerve impulse transmission. (Verma et al. 2014: 310)

Could do with more information on this mechanism.

Kumar, Sourav and Amal Chandra Mondal 2016. Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS Induced Model of Depression in Rat. Neurochemical Research 41(11): 3083-3094. DOI: 10.1007/s11064-016-2029-3

Hippocampus is the key limbic region where neurogenesis occurs in sub-ventricular zone (SVZ) throughout the life by influencing several environmental stimuli. The morphological changes occur in response to stress include hippocampal atrophy, loss of CA pyramidal neurons, reduction in hippocampal volume after exposure to chronic physical or psychosocial stress. (Kumar & Mondal 2016: 3083)

Note that CA neurons of the hippocampus is where dendritic arborization occurs.

BDNF is a neurotrophic factor responsible for neurite growth, differentiation and survival of neurons in the central nervous system. Studies indicate that AD treatment modulate behavioral depression by restoring the neurotrophic factors and hippocampal neurogenesis. Therefore, the present study indicates that normalization of HPA axis, induction of BDNF signaling and its interaction in hippocampal neurogenesis at least could provide a therapeutic approach for major depression. (Kumar & Mondal 2016: 3084)

In a later study, to which these authors contributed, it is said that "BDNF is the best characterized among all neurotrophins because of its role in synaptic plasticity and its potential role in the disease pathology or treatment of many psychiatric diseases" (Hazra et al. 2017: 75).

Detail investigation is required for finding out the mechanisms of action of herbal products as AD. Bacopa monniera is such an important phytochemical used for long time back because of its neurochemical benefits. (Kumar & Mondal 2016: 3084)

The plant species is a plant chemical?

Bacopa monniera (BM) (L.) Wettst (Brahmi, family: Scrophulariaceae) is one of the most extensively studied phytochemical commonly found as traditional Indian herbs mentioned in 'Ayurvedic materia medica' and used in the treatment of symptoms such as mental stress, psychiatric disorders, anxiety disorders, obsessive compulsive disorders, hysteria, epilepsy and insomnia and memory loss. (Kumar & Mondal 2016: 3084)

Yes, this one has an entry on "Brāhmī (Bacopa monnieri Pennell)" which says that "Brāhmī prevents aging. It promotes intellect, longevity and memory" (p. 53); and "Brāhmī, sarasvatī, somā, satyāhvā, brahma cārinī, maṇḍūka parṇī, mānḍūkī, tvaṣṭī, divyā, mahauṣadhī, kapota vaṅkā, munikā, lāvaṇyā and vallarī - these are synonymous." (p. 482).

Chronic administration of BME significantly enhanced the expression of BDNF (p<0.01) and DCX [neuronal marker doublecortin] (p<0.01) relative to CUS rats. (Kumar & Mondal 2016: 3090)

Affirming previous results.

Recurrent thoughts of death are a core symptom of major depression in humans, which reflects in rats during forced swimming test (Porsolt et al. 1978). Our findings revealed that CUS could significantly increase the immobility time in the FST and TST. This effect was reversed after chronic administration of BME. (Kumar & Mondal 2016: 3090)

The more I read about animal models the more dubious they seem.

Nuengchamnong, Nitra; Sontaya Sookying and Kornkanok Ingkaninan 2016. LC-ESI-QTOF-MS based screening and identification of isomeric jujubogenin and pseudojujubogenin aglycones in Bacopa monnieri extract. Journal of Pharmaceutical and Biomedical Analysis 129: 121-134. DOI: 10.1016/j.jpba.2016.06.052

Saponins found in B. Monnieri are dammarane steroidal saponin glycosides. These saponin glycosides are divided into 2 groups, jujubogenin and its isomeric pseudojujubogenin glycosides, which differ in the position of the phrenyl side chains of the aglycones. The glycosides have 1-4 units of arabinose and/or glucose attached to the C-3 position of the aglycone. Up to now, more than 20 saponin glycosides have been found in B. monnieri. [...] The mixture of four saponin glycosides i.e., bacoside A₃, bacopaside II, bacopasaponin C, and bacopaside X is called bacoside A. These four components along with bacopaside I are the major constituents in B. monnieri and are used as markers for quality control of B. monnieri preparations. Other compounds found in B. monnieri include phenylethanoid glycosides (bacopasides A, B, C), flavonoids (apigenin, luteolin, quercetin), alkaloids, and steroids. (Nuengchamnong, Sookying & Ingkaninan 2016: 121)

The quercetin glucoside was noted by Ramasamy et al. (2015), the other ones are new to me.

Luteolin and apigenin were purchased from Chromadex (CA, USA). (Nuengchamnong, Sookying & Ingkaninan 2016: 123)

So that's why some authors noted that quercitin was not available for purchase - other flavonoids are.

Sixty two components were detected and 53 of them including saponins, flavonoids, and phenylethanoids were tentatively identified by comparing the accurate mass and fragment information with the correlative reference data. This is the first systematic study on isomeric saponins in B. monnieri using the powerful LC-ESI-QTOF technique in both positive and negative ionization modes. Thirty new saponins with different core structures and sugar side chains were reported here for the first time. (Nuengchamnong, Sookying & Ingkaninan 2016: 133)

Still so much left to discover.

Sireeratawong, Seewaboon; Kanjana Jaijoy, Parirat Khonsung, Nirush Lertprasertsuk and Kornkanok Ingkaninan 2016. Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats. BMC Complementary and Alternative Medicine 16: Article 249. DOI: 10.1186/s12906-016-1236-4

It has recently been reported that B. monnieri extract has several pharmacological activities, e.g., a neuroprotective effect (Thomas et al. 2013; Saini, Singh & Sandhir 2012), ameliorating cognitive dysfunction (Le et al. 2013; Piyabhan & Wetchateng 2013; Piyabhan, Wetchateng & Sireeratawong 2013), increasing cerebral blood flow (Kamkaew et al. 2013), enhancing the activity of antioxidant enzymes and intracellular signaling pathways (Priyanka et al. 2012), an antiparkinsonian agent (Jadiya et al. 2011), reducing blood pressure (Kamkaew et al. 2011), hepatoprotection (Menon et al. 2010), anti-fertility (Singh & Singh 2009), anti-addiction (Sumathi et al. 2007 [online]), antioxidant (Russo et al. 2003; Pawar et al. 2001), antidepressant (Sairam et al. 2002), anti-stress (Chowdhuri et al. 2002 [Anti-stress effects of bacosides of Bacopa monnieri]), anti-ulcer (Sairam et al. 2001), anti-cancer (Elangovan et al. 1995 [In vitro studies on the anticancer activity of Bacopa monniera]), and anti-inflammation (Jain et al. 1994). (Sireeratawong et al. 2016: 1)

Very useful map to earlier studies.

Clinical studies have shown that B. monnieri reduces the rate of memory loss of newly acquired information (Roodenrys em>et al. 2002), improves memory performance in older persons (Morgan & Stevens 2010), and enhances cognitive performance in humans (Pase et al. 2011). (Sireeratawong et al. 2016: 1)

Likewise. And a probable source for the datum that "BM most effectively reduces the rate of forgetting, but not acquisition or other aspects of cognition" (Aguiar & Borowski 2013: 321).

However, B. monnieri was also shown to cause side effects in the gastrointestinal tract, i.e., nausea, increased stool frequency and abdominal cramps (Morgan & Stevens 2010). (Sireeratawong et al. 2016: 1)

One paper marked this down to the cholinergic system, but I suspect it has more to do with the serotonergic system.

Animals were weighed and observed daily for toxicological signs, physiological and behavioral changes, as well as mortality. The animals were anesthetized with an intraperitoneal injection of pentobarbital sodium at the end of the experiment. [...] Finally, the rats were sacrificed and their internal organs were excised, observed, weighed and fixed in 10% neutral buffered formaldehyde solution for further pathological examination. (Sireeratawong et al. 2016: 2)

More textual material for that short story.

A large single oral dose of B. monnieri extract (5,000 mg/kg) did not cause mortality in rats. Normal behavioral patterns were observed and no changes of eyes, skin, fur, mucous membranes, respiration, circulatory system, autonomic or central nervous system were found after that dose. The body weight on day 14 of the extract-treated rats had significantly increased compared to that of the control group. As shown in Table 2, the average lung weight of treated rats was significantly greater than in the control group, although physical appearance (color and texture) was normal. No significant histopathological change in the internal organs, including the liver and the kidney, were observed. (Sireeratawong et al. 2016: 3)

The enlargement of the lungs may have to do with the vasodilation effect.

B. monnieri extract did not cause any signs of toxicity or any other symptoms in the acute and chronic oral toxicity tests of both female and male rats. That indicates that B. monnieri extract is relatively non-toxic. Further study regarding the toxicology of this extract should be conducted in non-rodent species or in humans. (Sireeratawong et al. 2016: 9)

Good.

Gupta, Rupali; Akanksha Singh, Madhumita Srivastava, Vivek Singh, M. M. Gupta and Rakesh Pandey 2017c. Microbial modulation of bacoside A biosynthetic pathway and systemic defense mechanism in Bacopa monnieri under Meloidogyne incognita stress. Scientific Reports 7: Article 41867. DOI: 10.1038/srep41867

Utilization of medicinal plants for health consideration has become extremely popular with the indiscriminate use of synthetic drugs. Bacopa monnieri (L.) Pennell (family Scrophulariaceae), is second in the list of most essential Indian medicinal plants with ample number of therapeutically important bacosides (Gohil & Patel 2010). Bacoside A is [|] considered as a major active component known to have protective activities against morphine-induced cerebral toxicity, chemical-induced liver toxicity, and wound healing activity (Russo & Borrelli 2005; Sharma et al. 2015). The remedial properties are because of the presence of bioactive saponins synthesized via mevalonic acid (MVA) pathway (Vishwakarma et al. 2013 [online]). Globally, the requirement is met solely from the wild natural population of B. monnieri resulting in its listing as a threatened plant. (Gupta et al. 2017c: 1-2)

Wound healing activity is a first - haven't seen that before.

The impact of chitinolytic microbes on the expression of various genes. We next examined whether microbial inoculation enhanced bacoside A production through the modulation of biosynthetic pathway gene expression. The results indicated that plants primed with chitinolytic microbes showed the highest level of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), mevalonate diphosphate decarboxylase (MDD), and squalene synthase (SQS) transcription as compared to the control plants. Expectedly, the microbial combination of Chitiniphilus sp. and Streptomyces sp. treated plants showed induced level of HMGR (6.2 fold) and MDD (6.8 fold) transcription compared to the untreated pathogen stressed control plants. (Gupta et al. 2017c: 3)

It'd be nice to know a little more on the gene expression BM effects in humans.

It has been established that B. monnieri has two independent biosynthetic pathways; MVA occurring in the cytosol and the methyl-D-erythritol 4-phosphate (MEP) pathway in the plastid for triterpenoid saponins. The MVA pathway initiates with the acetyl-coenzyme A, which condenses into the acetoacetyl-Go A by the catalyzing action of acetyl-CoA acetyltransferase. Acetyl-coenzyme A is converted to isopentenyl diphosphate (IPP) through MVA, and HMGR (HMG-CoA reductase) which finally supplies carbon for the bacoside biosynthesis. (Gupta et al. 2017c: 6)

TBH I'm not sure what I'm looking at here.

For future applications, we suggest chitinase based formulations using chitinolytic microbes (that enhance plant growth rate, biomass and bacoside content) under natural conditions. Such microbial combination may not only provide a middle course by providing high productivity and protection coupled with high bacoside A but will also play a key role in dropping the cost of the expensive bacoside. (Gupta et al. 2017c: 7)

Is it really all that expensive?

Suganya, Mani; Shivaji Kavitha, Balasubramanian Mythili Gnanamangai and Ponnusamy Ponmurugan 2018. Phytofabrication of silver nanoparticles using Bacopa monnieri leaf extract and its antibacterial activity as well as oxidative stress-induced apoptosis of lung cancer. IET Nanobiotechnology 12(3): 318-324. DOI: 10.1049/iet-nbt.2017.0146

Recently, silver nanoparticles (AgNPs) have been shown in bionanomedicine because of their therapeutic applications in cancer as anticancer agents, in diagnostics and in probing. The mechanisms for AgNPs induced toxicity may be related to mitochondrial damage, oxidative stress, DNA damage, and induction of apoptisis. Different cell types hae been investigated for cytotoxicity of AgNPs, including NIH 3T3 fibroblast cells, HeLa cells and human glioblastoma cells. The therapeutic and diagnostic application of nanoparticles should not be toxic and biocompatible. Nanotechnology is a promising field of interdisciplinary research since it opens up a wide array of opportunities in different fields, including pharmacology, electronics, parasitology, and pest management. Nanoparticles and nanobiotechnologies have received considerable attention in recent years due to their wide range of applications in the fields of diagnostics, biomarkers, imaging, sensing, cell labelling, antimicrobial agents, drug delivery, cancer therapy, artificial implants, tissue engineering, pest management and masquito control. (Suganya et al. 2018: 318)

General education portion.

The plant-mediated biosynthesis (i.e. 'green synthesis') of metal nanoparticles is advantageous over chemical or physical, radiation, electrochemical and photochemical methods. Since it is less expensive, single step does not require highly toxic chemicals. Human beings are frequently infected by microorganisms such as bacteria, yeast, mould, virus, etc., silver and silver ion-based materials are treated with their bactericidal and fungicidal activities. Their antimicrobial effect is appropriate to the blockage of respiratory enzyme pathways, interacting with the sulphur-containing protein and modification of microbial DNA. (Suganya et al. 2018: 318)

BM "may disrupt enzyme system, disrupt genetic material of bacteria attacking on phospholipidbilayer cellular membrane" (Tanwar et al. 2016: 1942.

Bacopa monnieri (L.) commonly known as Neer-Brahmi, belonging to the family Scrophulariaceae is a creeping small prostrate annual herb found throughout the Indian subcontinent in wet, damp places near water logs and marshy areas. (Suganya et al. 2018: 318)

That's the common name in Tamil.

This plant is used as a memory vitaliser and treated with cardiac, respiratory and neuropharmacological disorders like insomnia, insanity, depression, psychosis, epilepsy and stress. It has a very important bearing on cancer treatment, as they can minimise the undesirable side effects of cancer chemotherapy, rendering the cancer cells more susceptible. It has been indicated that B. monnieri leaves can be executed as a supportive therapy dduring cancer chemotherapy, to minimise the toxic side effects of non-cancerous cells and to maximise the anticancer drug action. (Suganya et al. 2018: 318)

This makes sense, insofar as BM treatment can serve as a prophylactic against toxic agents. With alcohol, drinking alongside BM leads to an awful headache because toxic metabolites will stay in the system longer, whereas drinking alcohol after some time using BM leads to almost no hangover. That is, it might be a good idea to consume it for some time before chemo, probably not during.

Bioactive molecules of Bacopa monnieri coated in the AgNPs which generate free radicals caused membrane damage in cell membranes. (Suganya et al. 2018: 320)

Exactly the mechanism proposed above by the chicken nugget packers.

Similarly, AgNPs showed different levels of inhibition depending upon the Gram positive and Gram negative bacterial strains. The present reports clearly suggest that phytofabricated AgNPs may be effectively used as an antimicrobial agent for infectious disease management. (Suganya et al. 2018: 320)

Fancy word, that.

Kashyap, Suman; Neera Kapoor and Radha D. Kale 2015. Effect of vermicompost extracts on the in vitro micropropagation of Bacopa monnieri. International Journal of Green Pharmacy 9(1): 63-68. DOI: 10.4103/0973-8258.150930

Bacopa monnieri (Linn) Pennell (Scrophulariaceae) is widely distributed in tropical regions of Asia. It is widely used in the indigenous system of medicine. Many pharmaceutical and biotech companies have extended the term nutraceutical to include pure compounds of natural origin like "bacosides" from Bacopa monnieri. Today medicinal plants are important to the global economy, as approximately 80% of traditional medicine preparations involve the use of the extracts of the medicinal plants (Dhyani & Kala 2005). With increasing demand for herbal drugs, the natural populations of B. monnieri are threatened with overexploitation. (Kashyap, Kapoor & Kale 2015: 63)

Wiki says that a nutraceutical is a pharmaceutical-grade and standardized nutrient. Since they're not a regulatory category it's pretty easy to extend them to include medicinal compounds.

The results have indicated that, in general, the chemical supplements in the form of hormones, micronutrients or vitamins along with VC have a negative effect on the overall survival of plantlets. (Kashyap, Kapoor & Kale 2015: 66)

The more is not always the merrier.

Recently a report by the National Medicinal Plant Board, Government of India and Technology Information Forecasting and Assessment Counil has recommended immediate attention on some of the medicinal plants. Among which B. monnieri features prominently, bringing this in the category of highly endangered plants in India. (Kashyap, Kapoor & Kale 2015: 66)

No wonder there are so many recent studies on the micropropagation of BM.

Largia, Muthiah Joe Virgin; Lakkakula Satish, Rajaiah Johnsi, Jayabalan Shilpha and Manikandan Ramesh 2016. Analysis of propagation of Bacopa monnieri (L.) from hairy roots, elicitation and Bacoside A contents of Ri transformed plants. World Journal of Microbiology and Biotechnology 32: Article 131. DOI: 10.1007/s11274-016-2083-7

Bacosides are a complex mixture of structurally closely related glycosides of either jujubogenin or pseudojujubogenin present in the medicinal plant Bacopa monnieri (Murthy et al. 2006). Bacoside A, one among the bacosides of Bacopa, is a major chemical entity shown to be responsible for memory-facilitating action of this plant (Singh & Dhawan 1997). Due to its multipurpose therapeutic use and availability of many pharmaceutical products based on this plant extract, the need of B. monnieri is increasing steeply. Alternative and effective techniques need to be flourished for counter acting the market demand and to preserve the natural resources of this particular plant. (Largia et al. 2016: 1)

At this point I'm collecting variations of "memory-enhancing". Multipurposefulness refers to the long lists of positive health effects. And the commercial demand for it is naturally increasing along with the reports of its efficacy.

Agrobacterium rhizogenes, a soil bacterium of Rhizobicaceae family induces neoplastic growth of plant cells that differentiate to form "hairy roots" at the site of infection. Hairy roots are induced by the integration of a segment of bacterial DNA called transfer or T-DNA into the chromosome of the plant cell and its expression (Veena & Taylor 2007). They offer the interesting property of the easy regeneration of whole plants, avoiding callus formation and thus circumventing problems of somaclonal variation in a range of plant species. (Largia et al. 2016: 1)

In other words, these hairy roots are totipotent, able to regenerate the whole plant. For sake of self-justification, I'm reading these non-neurocognitive studies of this plant to gain some off-handed insight into the total context of its pharmacological use as much as out of general interest in the modern state of plant biology - these sorts of interesting tid-bits can be integrated into a biosemiotic treatment of human-plant-microorganism-environment interactions.

These plants show different morphological features such as wrinkled leaves, increased branching and rooting, shortened [|] internodes, reduced apical dominance and altered flowering (Tepfer 1990). More importantly, regenerated plants from hairy roots can produce higher levels of secondary metabolites. (Largia et al. 2016: 1-2)

Of course that's what the researcher is interested in (commercial application). From a biologically naive pespective, this makes sense insofar as the highest concentration of bacosides in normal plants was found in stolons (cf. Jeena et al. 2017: 2).

Wang et al. (2013) reported spontaneous regeneration of shoots from hairy roots in Salvia miltiorrhiza and Mehrotra et al. (2013) carried out the characterization of plants regenerated from hairy root cultures in Rauwolfia serpetina. In both the aforementioned studies, significant improvement in the accumulation of particular secondary metabolites has also been witnessed. In addition, this transformation system is ideal for the study of plant secondary metabolism and functional genomics (Sharafi et al. 2013). [↩] The strategy of eliciting the hairy roots which are the store house of phytochemicals has been now achieved for the enhanced production of phytoceuticals. (Largia et al. 2016: 2)

Funnily enough, just the previous paper argued that "nutraceutical" is not an appropriate term. Phytoceutical, I think, is.

For Bacoside A production, different concentrations of chitosan was added to 15 days old HR3 plants for 2 weeks. From HPLC estimation, it was observed that the HR3 plant extract has produced about 3.06% of Bacoside A which was 2.75 fold higher accumulation when compared to untransformed control plant extract. (Largia et al. 2016: 7)

Still only half of what the "elite" genotypes produce naturally (cf. Christopher et al. 2017: 80).

In order to further enhance the Bacoside A levels, the strategy of elicitation has been carried out. On quantification, elicitation with 10 mg/L chitosan has accumulated about 5.83% of Bacoside A which is two times higher than the content of un elicited cultures (3.06%) and fivefold higher than the untransformed controls (1.11%). (Largia et al. 2016: 7)

"In another report, the elicitation of B. monnieri cell suspension culture was performed using chitosan (100 mg/L) and the final concentration of bacoside A was found to be 34.77 μg/g DW which was 30-fold higher as compared to intact plant (Hegazi et al. 2017)." (Leonard et al. 2017: 10) - Whatever the ratio, at the end of the day adding chitosan is not as eco-friendly as cultivating chitinolytic microbes (Gupta et al. 2017a; 2017b; 2017c).

Dethe, Shekhar Michael; M. Lakshmi Deepak and Amit Agarwal 2016. Elucidation of Molecular Mechanism(s) of Cognition Enhancing Activity of Bacomind®: A Standardized Extract of Bacopa Monnieri. Pharmacognosy Magazine 12: 482-487. DOI: 10.4103/0973-1296.191464

Bacopa monnieri (L.) Wettst., (family: Plantaginaceae) also called Brahmi, is found throughout India. Many Indian traditional literatures like Athar-Ved, Charak Samhita and Susrutu Samhita have detailed the medicinal importance of B. monnieri. The traditional knowledge is aptly supported by modern scientific literature, which emphasizes the medicinal importance of B. monnieri. In addition to cognitive properties, B. monnieri has been reported to possess anti-ulcerogenic, anti-oxidant, adaptogenic, anti-anxiety, anti-depressant and hepatoprotective activities (Gohil & Patel 2010). It contains alkaloids (nicotine and herpestine), flavonoids (luteolin and apigenin) and saponins (bacoside A3, bacopaside I, bacopaside II, jujubogenin isomer of bacopa saponin C, bacopa saponin C). Various preclinical and clinical studies have reported B. monnieri to be effective in improving memory and cognition. It has shown significant reduction in forgetting the acquired information and improvement in memory acquisition and retention in healthy older individuals (Calabrese et al. 2008). (Dethe, Deepak & Agarwal 2016: 482)

Haven't noticed Athar-Ved before, though it is mentioned (cf. Singh et al. 2017: 121), the preferred transliteration for the latter two probably being Çaraka Samhita and Suśruta-Samhita (cf. Verma et al. 2014: 307). The fact that modern psychopharmacology concurs with traditional knowledge is what makes it all so interesting, tantalizing, even.

The potential of B. monnieri has also been studied as an anti-parkinsonian agent using C. elegans model (Jadiya et al. 2011), which signifies its importance in neurodegenerative disorders. Even though the role of B. monnieri as a memory and cognition enhancer has been accepted traditionally and proved in scientific literature with profuse evidences, the ambiguity about its mechanism of action still remains to be solved. we studied the effect of a methanolic extract of B. monnieri standardized to 40% bacosides, BacoMind™ (BM), on the different molecular targets associated with memory and cognition in order to understand its mechanism of memory enhancing action. (Dethe, Deepak & Agarwal 2016: 483)

This paper as a whole is an admirable step in the right direction but we're still far off, I think, from understanding the complete picture. Nevertheless, ambiguity is lessening.

Memory is not a unitary function as different memory and learning forms are sub served by different neurological pathways, which are closely interweaved with each other (Willingham 1997). The major neurological pathways that are involved in the memory and cognition include cholinergic, dopaminergic, serotoninergic pathway, and neuroprotective or antioxidant pathway (Aguiar & Borowski 2013). Among the serotoninergic pathway targets, downregulation of 5HT_2a, 5HT₃ (Roth, Hanizavareh & Blum 2004) and 5HT₅ receptors (Liu & Robichaud 2009) have been reported to improve memory. The inhibition of enzymes in the cholinergic pathway like acetyl cholinesterase (AChE) and butryl cholinesterase (BuChE), prevents the degradation of cholinergic neurotransmitters and improves the cholinergic transmission in the brain (Darvesh et al. 2003) helping to improve long-term memory processes. In the dopaminergic pathway, the inhibition of monoamine oxidase B (MAO-B), which breaks down monoamines like dopamine, has been found to be beneficial for memory and learning (Wong et al. 2010). Oxidative stress in the brain can impair memory and learning. Brain is susceptible to oxidative stress as it is a region with high metabolic activity and there are high levels of unsaturated lipids and pro-oxidant iron (Arivazhagan et al. 2002). (Dethe, Deepak & Agarwal 2016: 483)

Yup, not singular phenomena, i.e. "A randomized, double-blind study assessing changes in cognitive function..." (Mitra-Ganguli et al. 2017). These pathways are already somewhat familiar, though elsewhere they write about the "Elevation of the neurotransmitter 5-HT" (cf. Leung et al. 2017: 2). Could the oxidative stress release effect have something to do with how BM "chelates iron" (Chaudhari et al. 2017: 111)?

BM exhibited agonist effect on Canabinoid 1 (CB₁) receptors and the percent binding activity at 25 μg/mL with reference to control for 5-HT_2A and CB₁ receptors was found to be 33.3 ± 1.41% and 105.4 ± 0.42%, respectively. (Dethe, Deepak & Agarwal 2016: 483)

Could explain the anecdotal evidence of (recreational) cannabis going to waste when BM is in the system.

BM was found to inhibit COMT, an enzyme which controls dopamine metabolism by methylation and thereby modulates memory functions. COMT inhibitors like entacapone, are used as adjuncts to levodopa in the treatment of Parkinson's disease (Korlipara, Cooper & Schapira 2004). Since, COMT inhibition has been associated with prefrontal cortex dopamine signaling, this enzyme forms an important component of dopaminergic signaling pathway (Girault & Greengard 2004). Dopamine, which produces a stimulatory effect by acting on D1 receptors, stimulates the cAMP signaling pathway. BM could also be modulating the dopamine signaling pathway by inhibiting the activity of COMT enzyme. Bacosides from B. monnieri are reported to significantly increase the concentration of dopamine and serotonin in aged rat brains (Rastolgi et al. 2012). Thus, the potent inhibitory effect of BM on COMT enzyme could be corroborating its effect on memory and cognition via dopamine pathway. Studies have indicated that B. monnieri may prevent degeneration of dopaminergic neurons and increase the level of dopamine in cortex region of rat brain (Sheikh et al. 2007). Even though BM does not directly affect the other molecular targets like D1 receptor itself or the MAO-B, PP1 enzymes of the dopamine signaling pathway, our studies indicate that it could be exerting a protective effect an enhancing the dopaminergic system by increasing the concentration of dopamine, a catecholamine required for long-term memory, by inhibiting the COMT enzyme. (Dethe, Deepak & Agarwal 2016: 486)

It would appear that in acts upon the dopaminergic system in a manner similar to the effect on another pathway: "It is expected that decreased AChE activity may enhance cholinergic activity by raising AChE level (inhibition of metabolism), thereby maintaining/improving cognitive functions" (Mishra, Mishra & Jha 2018: 150).

The synthesis and release of neuropeptides arginine, vasopressin, substance-P, oxytocin and angiotensin II are known to strongly influence the learning and memory process (Gülpinar & Yeğen 2004). BM, when tested for its inhibitory activity against two neuropeptidases; prolyl endopeptidase (PEP) and insulin-regulated aminopeptidase (IRAP), was found to inhibit the activity of PEP enzyme which is known to cleave short peptides with internal proline residues (Wilk 1983). PEP degrades the neuropeptides arginine-vasoprossin, oxytocin, neurotensin and substance-P that play a key role in positive reinforcement, social interactions, emotions and stress responsivity (Maes et al. 1999). PEP has been acknowledged for its role in cognitive impairment (D'Agostino et al. 2013). Reduced PEP activity amplifies substance P-mediated stimulation of Ins (1,4,5)P₃ that stimulates the release of intracellular calcium, known to cause neurotransmitter release (Mikoshiba 1993). The effect of reduced PEP activity on calcium concentration is a novel intracellular function of this peptidase, that has an impact on the cognitive enhancement (Schulz et al. 2002). (Dethe, Deepak & Agarwal 2016: 486)

This pathway is indeed novel. This is the only paper in current collection mentioning it. What is familiar is the cellular calcium ion homeostasis: "Once the cell is depolarised, NMDA receptors and voltage gated calcium channels (VGCC) on the post-synaptic membrane allows the inflow of calcium ions (Ca²⁺) into the intracellular space" (McPhee et al. 2016: 73).

BM exerted significant antagonist effect on 5-HT₆ receptors, which is an important component of serotonergic pathway. A growing body of evidence suggests the use of 5-HT₆ antagonists for treating cognitive dysfunctions (Marcos et al. 2010) and BM exhibited significant antagonism at these receptors with an IC₅₀ value of 52 ± 1.2 μg/mL. Also, 5-HT₆ receptor blockade has been reported to enhance cholinergic and glutaminergic neurotransmission (Woods et al. 2012) and increase dopamine level (Doleviczényi et al. 2008). Thus, BM with an antagonistic effect on 5-HT₆ receptor could be affecting memory and cognition in more than one way. (Dethe, Deepak & Agarwal 2016: 486)

Hence gradiloquent phraseology like "multi-pharmaceutical utilization" (Al-Hasawi 2017: 33) and "multifunctional herbals" (Srimachai et al. 2017: 2).

BM also had significant antagonistic effect on 5HT receptor subtype 2A. 5HT_2A receptor antagonists have been suggested to be beneficial for memory and cognition and have been implicated in insomnia (Landholt & Wehrle 2009) and also reported to increase sleep intensity. Morairty et al. (Morairty et al. 2008) have presented the effect of sleep promotion via 5-HT₆ receptor blockage. So, the change in sleep intensity because of 5HT_2A antagonism may improve cognition and vigilance during wakefulness. (Dethe, Deepak & Agarwal 2016: 486)

This is where I personally disagree, at least on the face of it, since my experience attests to sleep becoming very light, i.e. vigilance and wakefulness during sleep. All in all an excellent paper, one of the best in what I've read on this subject, if not the best thus far.

Naik, Poornananda Madhava; B. R. Patil, Kavita B. Kotagi, A. M. Kazi, H. Loxesh and S. G. Kamplikoppa 2014. Rapid one step protocol for in vitro regeneration of Bacopa monnieri (L.). Journal of Cell & Tissue Research 14(2): 4293-4296.

Brahmi is considered as the main rejuvenating herb for nerve and brain cells and, therefore, has played a very important role in ayurvedic therapies for the treatment of cognitive disorders of aging. (Naik et al. 2014: 4293)

"Brāhmī prevents aging. It promotes intellect, longevity and memory" (Dash & Kashyap 1980: 53) - In: Dash, Vaidya Bhagwan and Vaidya Lalitesh Kashyap 1980. Materia Medica of Ayurveda: Based on Ayurveda Saukhyam of Tadarānanda. New Delhi: Concept Publishing Company.

In the present study, a rapid and reliable in vitro regeneration protocol was developed for Bacopa monnieri by using 2.0 mg/1 KN [kinetin] as a single hormone. This protocol is novel because of its minimal requirements and cost effectiveness for propagation. (Naik et al. 2014: 4296)

"Kinetin is a type of cytokinin, a class of plant hormone that promotes cell division. Kinetin was originally isolated by Miller and Skoog et al. as a compound from autoclaved herring sperm DNA that had cell division-promoting activity." (Wikipedia) - Still not as eco-friendly as chitinolytic microbes.

Jasim, B.; K. S. Sreelakshmi, Jyothis Mathew and E. K. Radhakrishnan 2016a. Surfactin, Iturin, and Fengycin Biosynthesis by Endophytic Bacillus sp. from Bacopa monnieri. Microbial Ecology 72: 106-119. DOI: 10.1007/s00248-016-0753-5

The metabolome of endophytic microbiome plays an important role in biotic and abiotic stress tolerance, disease resistance, and growth promotion of a host plant. This makes the biodiversity richness and biosynthetic versatility of endophyte as a valuable source of medicinal natural products. The unique chemical environment of medicinal plants may likely have a selective approach for accommodating biosynthetically complex endophytes. Endophytic production of a structurally diverse antifungal chemical scaffold is always attractive to plants to meet the challenges generated by phytopathogenic fungi. So the identification of these endophytes can have immense applications as biocontrol agents to prevent plant diseases in an eco-friendly approach. (Jasim et al. 2016a: 106)

Metabolomics is the scientific study of chemical processes involving metabolites. This selectivity comes to the fore in the finding that some endophytes may produce bacosidic metabolites (Jasim et al. 2017).

Among the various plants that have been studied for endophytes, medicinal plants are considered to have highly efficient endophytic bacterial isolates with biocontrol properties. Therefore, the study selected Bacopa monnieri (L.) as a source for isolation of endophytic bacteria. The plant is commonly known as "Brahmi" or Indian water-hyssop which has been used in traditional medicinal formulations for the treatment of neurologic and gastrointestinal disorders and is also used as a hepatoprotective, antidepressant, and antioxidative agent. (Jasim et al. 2016a: 107)

Otsetõlkes: India vesi-iisop. // As an aside (or meta?) this made me wonder how BM is an opportune plant to read up on, as researchers are more bothered by and drawn to study medicinal plants than probably any other type, making it an ideal vehicle for finding out about the newest study methods.

Even though there are various methods for plant disease control that have been carried out for many years, use of endophytic microbes for the control of plant disease have much applications. However, the challenge for the wide use of bacteria for the control of plant disease protection is their low ability to sustain in the natural environment as well as to colonize diverse plants. But with the use of endophytic microbes that have the adaptation mechanisms for colonizing diverse plant tissues, they can be expected to have better survival efficiency for longer periods in the plant and, thereby, long-term protection of the plant to resist disease. (Jasim et al. 2016a: 113)

What I gather from the agar images in this paper, they don't propagate very effectively in potato dextrose, though this could be due to the crude methanolic extract. Below, it reads that "Studies of anti-phytopathogenic properties of endophytic Bacillus sp. from diverse host plants have been gaining interest recently due to its ability for fast colonization and their ability to retain in the natural environment for longer time" (ibid., 114), so I'll mark this down to my microbiological illiteracy.

Yadav, Sheetal; Poojadevi Sharma, Anshu Srivastava, Priti Desai and Neeta Shrivastava 2014. Strain specific Agrobacterium-mediated genetic transformation of Bacopa monnieri. Journal of Genetic Engineering and Biotechnology 12(2): 89-94. DOI: 10.1016/j.jgeb.2014.11.003

Bacopa monnieri, a well known medicinal plant of Indian system of medicine, has recently gained interest as a potential host system for expression of foreign proteins. The plant has high regeneration response and a large number of pharmacological and clinical studies have indicated that this plant is non toxic for human consumption. These valuable features make B. monnieri a well suited plant to be explored as a model host plant for foreign protein production. (Yadav et al. 2014: 89)

Phraseology in line with analogues like "adventitious roots at almost every node" (Christopher et al. 2017: 76) and increasing the "initial projections or 'budding' of dendrites" (McPhee et al. 2016: 73).

Considering the underexplored potential of B. monnieri to act as a suitable host system for foreign protein expression, we attempted to evaluate the genetic transformation susceptibility of B. monnieri to three strains of Agrobacterium tumefaciens and effect of this interaction on level of foreign protein β-glucuronidase (GUS) expression. GUS gene was chosen as transgene for the study on account of the fact that its expression in genetically manipulated plant can be visually detected with histochemical assay with high sensitivity. (Yadav et al. 2014: 90)

Though what is needed is an increase production of "native" chemical compounds or secondary metabolites (e.g. Leonard et al. 2017 and Gupta et al. 2017a).

Bansal, Mahima; Anil Kumar and M. Sudhakara Reddy 2015. Production of bacoside A, a memory enhancer from hairy root cultures of Bacopa monnieri (L.) Wettst. Journal of Applied Research on Medicinal and Aromatic Plants 2(3): 92-101. DOI: 10.1016/j.jarmap.2015.05.001

Cognitive deficits that are present with various neuropsychiatric conditions or developmental deficits require nootropics to boost cognitive abilities (Kulkarni et al. 2012). Number of natural compounds with nootropic effect has been identified from several plants (Das et al. 2002). One such plant that has been used since almost 3000 years as brain tonic for improvement of cognition is Bacopa monnieri (Russo & Borrelli 2005). It is mentioned in the traditional Ayurvedic treatises including the Caraka Samhita (6th century A.D.) and the Bravprakash Var-Prakarana (16th century A.D.) for improving memory and treatment of anxiety (Govindrajan et al. 2005; Prasad et al. 2008). In addition, it is also used for treatment of cardiac, respiratory and neuro-pharmacological disorders (Russo & Borrelli 2005; Nadkarni 1976 [Indian Materia Medica]). The pharmacological properties of B. monnieri are mainly attributed to the saponins called 'bacosides' (Singh & Dhawan 1997). (Bansal, Kumar & Reddy 2015: 92)

Found no useful further information about Bravprakash Var-Prakarana online, only various iterations of this same paragraph, almost word-for-word, in different papers.

The maximum biomass and bacoside A content was observed when the cultures were grown for 25 days compared to longer incubation. The bacoside A content and biomass decreased with increase of time. The decline in bacoside A content after 25d of cultivation could be explained by a low production rate and initiation of degradation process. (Bansal, Kumar & Reddy 2015: 95)

Could also be explained with the native function of bacosides in BM, on which I still haven't found anything. (Are researchers even interested in what these metabolites do in the plant itself?) By crude analogy, one would guess that they have something to do with the "adventitious" growth of shoots.

Katoch, Meenu; Aseem Salgotra and Gurpreet Singh 2014. Endophytic fungi found in association with Bacopa monnieri as potential producers of industrial enzymes and antimicrobial bioactive compounds. Brazilian Archives of Biology and Technology 57(5): 714-722. DOI: 10.1590/s1516-8913201402502

In recent times, there has been increasing demand for the products from more sustainable sources and to avoid synthetic molecules, which is essentially driven by the increasing health consciousness of the society. Similarly, focus is also towards the microbes to find the bioactive molecules (Strobel & Daisy 2003). The establishment of higher plants in their respective habitats involves a capacity to interact with different organism. The term endophytic fungus is used to describe those fungi that can be detected at a particular moment within the tissues of an apparently healthy plant host. (Katoch, Salgotra & Singh 2014: 714)

Sociobiosemiotic interactions: society demands natural medicines, researchers are disposed towards studying medicinal plants and their interactions with other living organisms, primarily microorganisms.

The endophytic fungi associated with the medicinal plants not only produce antibacterial molecules but also many other pharmacologically active substances with a potential to act as antitumor agents (Pestalotiopsis microspora, taxol), antifungar agents (Cryptosporiopsis criptocandina, quercine). Endophytes are also known to produce the factors of plant growth, toxins and enzymes. Some endophytes are also used as biological controllers of many diseases and plaques (Strobel 2002). (Katoch, Salgotra & Singh 2014: 714)

Like that study of the biosynthetic potential of endophytic Aspergillus sp. to produce bacopaside N1 (Jasim et al. 2017). It'd be very interesting to find out, in that case, if microorganisms are able to "learn" to produce the plant's secondary metabolites from living within the plant.

Bacopa monnieri (L.) Pennell (Scrophulariaceae), commonly known as "Brahmi" or Indian water hyssop is commonly found in Asia, Australia, and AMerica. Since time immemorial, Brahmi has been used in ayurvedic formulations for treating gastrointestinal and neurologic disorders. Previous studies have proved that its active constituent bacosides enhances the efficiency of nerve impulse transmission leading to improved memory related functions (Mahato, Garai & Chakravarty 2000; Chakravarty et al. 2001; 2003; Hou et al. 2002; Russo & Borrelli 2005). (Katoch, Salgotra & Singh 2014: 715)

Could do with more information about the mechanism of action behind improved nervous impulse transmission.

There are no previous reports on the isolation and cultivation of endophytes from Bacopa monnieri. Therefore, the current study was undertaken to isolate, and screen endophytic fungi from Bacopa monnieri with antibacterial activities and also to determine their ability to produce enzymes that could be exploited industrially. (Katoch, Salgotra & Singh 2014: 715)

Forgot to put "to the best of our knowledge" in there, so if I'm going to find earlier reports on endophyte isolation in BM I'm not going to let you forget it.

Endophytes were identified on the basis of characteristics such as the structure of hyphae, conidia, and conidiphores. Conidiophore structure and morphology were described by obtaining them from the edge of conidiogenous pustules or fascicles during maturation of conidia, which usually occurred after 4-7 days of incubation. (Katoch, Salgotra & Singh 2014: 715)

Interesting word, having a double meaning: "a separately published instalment of a book or other printed work" and "a bundle of structures, such as nerve or muscle fibres or conducting vessels in plants".

All the endophytic fungal isolates produced protease or/and lipases, which suggested that they might be of relevance as bio-control agents. The genetic machinery required to produce cell wall degrading enzymes such as cellulase, may already be present in endophytic fungi prior to the establishment of the symbiotic relationship with the host plant. From an evolutionary perspective, these endophytic fungal strains may have adapted to the respective metabolic machinery of the host tissues to produce biomolecules not only important for their own biology, but also for the host plant's requirements. (Katoch, Salgotra & Singh 2014: 719)

Interesting suggestion, though the biomolecules in question here are "natural products for protecting the plant host against the pests and pathogens" (ibid., 721) and not necessarily the secondary metabolites we're interested in.

Singh, Babita; Shivani Pandey, Rajesh Verma, Jamal Akhtar Ansari and Abbas Ali Mahdi 2016. Comparative evaluation of extract of Bacopa monnieri and Mucuna pruriens as neuroprotectant in MPTP model of Parkinson's disease. Indian Journal of Experimental Biology 54(11): 758-766.

Parkinson's disease (PD) is the second most frequent neurological disorder, characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN) region of ventral midbrain, causing a consequent reduction of dopamine (DA) levels in the striatum. Loss of dopamine supply to striatum causes imbalance with neurotransmitters like acetylcholine and DA, resulting in PD symptoms. Four typical characterestic symptoms observed in PD patients are akinesia, dyskinesia, rigidity and tremor. The three main strategic developments in drug discovery for therapeutic management of PD patients have focused on the alleviation of motor symptoms using dopaminergic mimetics; the development of novel non-dopaminergic drugs for symptomatic improvement; and the discovery of neuroprotective compounds that have disease modifying effects in PD. (Singh et al 2016: 758)

"BM could also be modulating the dopamine signaling pathway by inhibiting the activity of COMT enzyme. Bacosides from B. monnieri are reported to significantly increase the concentration of dopamine and serotonin in aged rat brains" (Dethe, Deepak & Agarwal 2016: 486).

Currently, there is no therapy clinically available that delays the neurodegenerative process itself, and therefore modification of the disease course via neuroprotective therapy is an important unmet clinical need. Thus, understanding the pathophysiology and etiology of the disease at cellular and molecular levels and finding molecular targets for neuroprotective/disease-modifying therapy is the crucial issue in the field of basic PD researche. "Neuroprotection" aims to slow down the disease progression and secondary injuries by halting the loss of neurons or may be by promoting generation of new neurons (neurogenesis) which has not been explored in PD. (Singh et al 2016: 759)

In other words, BM could be used as a "prophylactic" against neurodegenerative diseases. I've noticed that some reduce "neuroprotection" to oxidative stress management but I think it should include the variety of mechanism demonstrated to be operative in BM treatment.

Locals from Assam, India used Brahmi to treat memory loss since ages (Bhattacharjya et al. 2015). B. monnieri is also known to possess antioxidant properties due to sulfhydryl and polyphenol components that scavenge ROS. BM extract, bacoside compounds in particular, have been investigated extensively for neuropharmacological activities (Paulose et al. 2008). (Singh et al 2016: 759)

"The presence of endogeneous antioxidants, such as polyphenols and sulfhydril groups, may contribute to BmE's antioxidant effects." (Dhanasekaran et al. 2007: 968)

Mucuna pruriens (L.) DC, commonly called Velvet bean or cowhage, is popular in India and China for treatment of Parkinson's disease. Apart from its use as aphrodisiac and in snakebite, it is also known for treating ulcer as well as psychological disorder. While tribals from Malda, West Bengal use it as a sex stimulant, locals in Rajasthan feed camels along with jaggery or wheat bread to bring them into heat. M. pruriens seeds contain significant amounts of levodopa. The endocarp of M. pruriens is non-toxic and is 2-3 times more potent than synthetic levodopa. M. pruriens has also shown to exhibit neuroprotective effect by increasing brain mitochondrial complex-I activity and significantly restoring dopamine and nor-epinephrine levels in Parkinsonism animal model. (Singh et al 2016: 759)

Familiar already from a study of multiherbal treatments (cf. Kean, Downey & Stough 2017: 14), where levidopa was designated as L-DOPA, "the precursor to dopamine neurotransmitters". The seeds sound, by description, like the mega seeds in Rick and Morty.

We studied the comparative effect of BME [B. monnieri or MPE [M. pruriens} treatment on the mRNA expression of neurogenic genes/neuronal transcription factors in the substantia nigra region of brain. A significant change was found in neurogenic genes/transcription factors including neurogenin and DCX [doublecortin] in MPTP[neurotoxin]+BME treated group compared to control. MPE also altered the expression of neurogenic genes in substantia nigra region of brain. Neurogenin is basic helix-loop-helix (bHLH) family proneural transcription factor, which acts as master regulator of neuronal differentiation. It is involved in the differentiation of nervous system. The DCX is a marker of newborn neurons. MPTP+BME treated groups significantly upregulated the expression of neurogenic genes as compared to control group. However, in comparative study of MPTP+BME and MPTP+MPE, BME showed significant change. (Singh et al 2016: 762)

Is this evidence that BM promotes neurogenesis? Sadly, in the papers I've downloaded thus far, DCX appears only in Kumar & Mondal (2016), and neurogenin in none.

Our findings shows that BME can be a better neuroprotectant as it has significant effect on retention of locomotor activity, preventing neurodegeneration and promoting neurogenesis as compared to MPE. It is also pertinent to note that biotechnologists have already developed improvised methods including bioreactor systems for improved biosynthesis of bacoside (Sharma et al. 2015). (Singh et al 2016: 763)

I definitely need to know more about the mechanisms of neurogenesis. Also, this must be one of the very few animal experimentation papers that cares to mention the work conducted in the biotechnological sector (e.g. every other paper here).

Dopaminergic neurons provide fertile environment for the generation of ROS, as the metabolism of DA produces hydrogen peroxide and superoxide radicals, and auto- oxidation of DA produces DA-quinone, a molecule that damages proteins by reacting with cysteine residues, so [|] effective antioxidant agents capable of augmenting the intracellular concentrations of these species should be present. (Singh et al 2016: 763-764)

Contrary to the many, many, many instances of ROS damage reported in this literature (causing everything from male infertility to refrigerated chicken nugget spoiling), this makes sense.

BME and MPE both showed neuroprotective effect on dopaminergic neurons, which could be a result of its promising antioxidant capacity, but BME showed a better effect as compared to MPE, the reason for the same can be explained as M. pruriens seeds are rich source of L-DOPA and its metabolites. Therefore, increase in dopamine level in the brain with M. pruriens seed extract treatment may cause increase in the oxidative stress, and increased activity of antioxidants may not suffice to combat increased free radical damage. (Singh et al 2016: 764)

By this token dopaminergic mimetics are actually pretty bad, and so should BM be, as it, too, "increase[s] dopamine level" (Dethe, Deepak & Agarwal 2016: 486). I have a feeling that once again too much emphasis is put on oxidative stress. Going by this literature, ROS is pretty much the only bad thing (for the CNS) out there.

Neurogenin, in addition to promoting neurogenesis, maintains progenitor cells in an undifferentiated state, allowing them to proliferate prior to maturation and also inhibits astrocyte differentiation by inhibiting the Stat pathway (Sun et al. 2001). DCX is a marker for immature neurons and neuroblasts and is expressed specifically in migrating neuronal precursors/neuroblasts in the brain. (Singh et al 2016: 764)

Well that's a starting point as good as any to get into neurogenesis.

Roshni, L. S.; A. Gangaprasad and E. A. Siril 2014. Evaluation of variability in Bacopa monnieri (L.) Pennell using morphological and biochemical markers. International Journal of Applied Research in Natural Products 7(2): 25-31.

B. monnieri is renowned in the Indian system of medicine (Ayurveda) as nervine tonic for promoting mental health and improving memory. This herb is also reported to possess hepatoprotective (Vikayan & Helen 2007), anti-cancer (Rohini & Devi 2008), [|] antioxidant (Chowdhury et al. 2002), anti-ulcer (Sairam et al. 2001), anti-inflammatory (Viki & Helen 2008) properties and counteracting effect on oxidative stress (Dhanasekaran et al. 2007). (Roshni, Gangaprasad & Siril 2014: 25-26)

Going by the sources I've already accumulated this list could be ten times as long.

Due to the medicinal potential and consequent commercial importance, B. monnieri has been identified as one of the major priority species of medicinal plants for further research and development (Karki & Williams 1999). B. monnieri have been so far harvested almost exclusively from natural habitats. The annual requirement for this plant was estimated recently as around 12,700 tons of dry biomass and therefore, as in the case of many other medicinal plants, the development of suitable cultivation technique appears indispensable to prevent depletion of resource base in the natural stands. [...] The present study was undertaken to facilitate organized cultivation of B. monnieri. It is also intended to select the superior eco-types for their use in breeding programmes and mass propagation. Accessions from different parts of Kerala state were characterized morphologically and biochemically for the assessment of naturally occurring variability among different accessions. (Roshni, Gangaprasad & Siril 2014: 26)

The tonnage has probably increased by quite a large margin in the past four years. Superior eco-types = elite genotypes (cf. Christopher et al. 2017).

The superiority of total saponin content and bacoside in the BM 9 accession possibly [|] attributes to genetic distinction in this accession compared to other collections. In this regard further studies needs to be undertaken to depict genetic variation among accessions using molecular markers. Based on superiority of total saponin and other desirable traits such as leaf length and internodal length, the accession BM 9 elevated as superior accession having the potential to use in the vegetative multiplication and improvement programmes. [...] Botanists have usually made distinction within species using morphological markers which leads to effective identification of morphologically distinct types from various collections. In the present work such an effort has brought about an account on level of morphological variations in B. monnieri collections and screening of superior germplasm. However, morphological parameters can be influenced by the genetic and environmental factors. Therefore, further extension to identify genetic basis for the morphological variability and superiority of germplasm is to be elucidated. (Roshni, Gangaprasad & Siril 2014: 29-30)

According to Table 6, accession BM 9 (from Marikkunnu, Kozhikkode) had total saponin content of 81.4 mg/g DW and bacoside content 36.41 mg/g DW, which is significantly higher than the elite genotypes found by Christopher et al., which were around 5-6% DW.

Ramasamy, Seetha; Lik Voon Kiew and Lip Yong Chung 2014. Inhibition of Human Cytochrome P450 Enzymes by Bacopa monnieri Standardized Extract and Constituents. Molecules 19(2): 2588-2601. DOI: 10.3390/molecules19022588

Bacopa monnieri (Linn.) Pennell (Scrophulariaceae), also known as brahmi in Ayurvedic medicine, has been used in traditional and Ayurvedic medicine for centuries as a brain tonic to ehnance learning and memory and to improve concentration. These traditonal claims have been supported by several preclinical and clinical studies (Stough et al. 2001; Roodenrys et al. 2002; Calabrese et al. 2008; Barbhaiya et al. 2008), and the observed cognitive effects have been attributed to bacoside A (Singh et al. 1988; Dhawan & Singh 1996; Singh & Dhawan 1997), which is a mixture of four triglycosidic saponins (bacoside A3, bacopaside II, bacopaside X and bacopasaponin C) (Deepak et al. 2005). (Ramasamy, Kiew & Chung 2014: 2589)

"The traditional knowledge is aptly supported by modern scientific literature, which emphasizes the medicinal importance of B. monnieri." (Dethe, Deepak & Agarwal 2016: 482)

A reputable nootropic agent and the second most highly touted herb in Ayurveda (Russo & Borrelli 2005, Van Murthy et al. 2010), B. monnieri is widely marketed and used not only in India but also in the international market. Since B. monnieri is used as a neuropharmacological agent, the chances of chronic or recurrent usage of B. monnieri-related products by patients with mental illnesses are very high. These patients are also most likely to be prescribed therapeutic drugs, raising the potential for herb-drug interaction. (Ramasamy, Kiew & Chung 2014: 2589)

Sensible. There is also the nootropic community, where BM is consumed alongside a variety of other substances that are not prescribed therapeutic drugs but may nevertheless involve a variety of herb-drug interactions.

These interactions may occur through the inhibition or induction of hepatic and intestinal drug-metabolizing enzymes (e.g., CYPs) and transporters (e.g., p-glycoprotein) (Zhang et al. 2010). CYP-mediated drug interactions are a major concern because CYP enzymes are involved in phase 1 metabolism of more than 70% of prescription drugs (Tyagi et al. 2010). Inhibition of a CYP enzyme causes an increase in drug plasma levels through decreased drug metabolism, which could result in significant adverse reactions or toxicity. The introduction of CYP enzymes leads to a decreased drug plasma and drug efficacy. (Ramasamy, Kiew & Chung 2014: 2589)

I definitely need to know more about this to evaluate the threat of taking recreational drugs alongside BM.

B. monnieri extract was found to exhibit moderate inhibition against CYP2C19, CYP2C9, CYP1A2, and CYP3A4 and weak inhibitory activities against CYP2D6, with most potent inhibition on CYP2C19 (IC₅₀ = 23.67 ± 2.84 μg/mL). (Ramasamy, Kiew & Chung 2014: 2591)

According to Wikipedia, CYP2C19 "is involved in the metabolism of xenobiotics, including many proton pump inhibitors and antiepileptics" and "acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix) also drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam." - Somewhat ironic that BM shuts off enzymes for ulcer and epilepsy medications, seeing as these are the non-memory-related domains where it shows most therapeutic potential.

Due to the traditional popularity of B. monnieri as a brain tonic and the suggested use for Alzheimer's diseasy (AD) (Uabundit et al. 2010), anxiety (Bhattacharya & Ghosal 1998), depression (Sairam et al. 2002) and epilepsy (Mathew et al. 2010), mental disorder patients who are on prescription drugs might use B. monnieri as an alternative medicine, and some prescription drugs that are used for AD, anxiety, depression and epilepsy are metabolized by CYP2C19, CYP2C9, CYP1A2, and CYP3A4. (Ramasamy, Kiew & Chung 2014: 2596)

At some point I searched EBSCO with BM and these keywords to choose 10 from each for future reading, but this current tactic of going by whatever EBSCO serves up seems to work just as fine as long as I also include works cited. // The general question this inspires is, what effect does BM have on metabolism in general (e.g. food, caffeine, nutrients, etc.) when taken chronically?

Le, Xoan Thi; Hang Thi Nguyet Pham, Tai Van Nguyen, Khoi Minh Nguyen, Ken Tanaka, Hironori Fujiwara and Kinzo Matsumoto 2015. Protective effects of Bacopa monnieri on ischemia-induced cognitive deficits in mice: The possible contribution of bacopaside I and underlying mechanism. Journal of Ethnopharmacology 164: 37-45. DOI: 10.1016/j.jep.2015.01.041

Dementia is characterized by the global loss of cognitive ability resulting secondary to many neurodegenerative disorders. Aging is a major risk factor for dementia, which includes various types, such as vascular dementia, frontotemporal degenerative dementia, Lewy body dementia, and Alzheimer's disease. Vascular dementia represents the second most common cause of dementia after Alzheimer's disease (AD) in the elderly, and is referred to as the "silent epidemic of the twenty-first century" (Battistin & Cagnin 2010). (Le et al. 2015: 37)

General education portion.

However, to the best of our knowledge, information on the biochemical activities of each bacoside and their contribution to the actions of BM is still very limited. (Le et al. 2015: 38)

True indeed.

We previously reported that the BM treatment inhibited the ex vivo activity of cholinesterase in the brain (Le et al. 2013) and that the cholinesterase inhibitor THA, via the endogenous ACh stimulation of muscarinic receptors, protected NMDA-induced neuronal damage in OHSCs (Inada et al. 2013). Thus, we next determined whether a cholinergic system was involved in the neuroprotective effects of bacopaside I on OGD-induced neuronal cell damage. The administration of SCP (30 μM), a muscarinic receptor antagonist, or MEC (30 μM), a nicotinic receptor antagonist, failed to block the neuroprotective effects of bacopaside I in this in vitro ischemia model. This result excluded the passibility that, similar to tacrine, the stimulation of acetylcholine receptors, particularly muscarinic receptors, could be involved in the neuroprotective effects of bacopaside I. (Le et al. 2015: 42)

So, the "crucial role of muscarinic receptors in the action of B. monnieri" (Ramasamy et al. 2015: 14) is not as crucial as reported?

On the other hand, the neuroprotective effects of bacopaside I were significantly blocked by the PI3K inhibitor LY293002 (30 μM), suggesting the involvement of PI3K/Akt signaling in the effects of bacopaside I. (Le et al. 2015: 42)

"The phosphatidylinositol 3-kinase (PI3K) pathway activates serine/theonine kinase and the mitogen-activated protein kinase (MAPK) or extracellular signal regulated kinase (ERK) pathway activate several downstream effectors. Each of these signaling pathways confers the unique function of BDNF on cells." (Hazra et al. 2017: 75)

Recognition memory refers to the ability to judge a previously encountered item as familiar and depends on the integrity of the medial temporal lobe. The ORT [object recognition test] test has become popular for rodents and is currently a benchmark task for assessing recognition memory, in which the hippocampus and perirhinal cortex play critical roles. (Le et al. 2015: 43)

Memory systems are much more to my liking than high neurology (looking forward to neurocognitive experiments where normal memory, instead of various neurodegenerative diseases, are in focus). Also, ATM machine and PIN number - "ORT test" is an example of the RAS syndrome.

Taken together, the present results further support the anti-dementia effects of BM. However, we cannot exclude the possibility that BM directly affected the decrease of the cerebral blood flow during an ischemic period and thereby exhibited apparently the neuroprotective effects against ischemia-induced cognitive deficits since, in the present study, the treatment with BM was started before the induction of the ischemic lesion. This possibility remains to be examined. (Le et al. 2015: 43)

Wait, doesn't BM increase cerebral blood flow? E.g. "The neuroprotective effect of EBm is also due to nitric oxide-mediated cerebral vasodilation" (Chaudhari et al. 2017: 111); BM "increased the cerebral blood possibly contributing to their nootropic and neuroprotective action" (ibid., 117); BM "increased cerebral blood flow without changing blood pressure" (Srimachai et al. 2017: 2); BM "increased cerebral blood flow" (Ramasamy et al. 2015: 2), etc.

Our results demonstrated that bacopaside I exerted more potent neuroprotective effects against OGD-induced neuronal cell damage than bacopaside N2 and a mixture of bacopaside II and bacopasaponin D. The treatment with bacopaside N2 and a mixture of bacopaside II and bacopasaponin D failed to reduce OGD-induced neuronal cell damage under this experimental condition. Comparisons of the chemical structures of these bacosides allowed us to infer that the glycoside moiety of bacopaside I played an important role in its anti-ischemic effects on OHSC_S since the main difference observed in [|] chemical structures of bacopaside I and the three other bacosides was a sulfate group on the sugar moiety of bacopaside I. (Le et al. 2015: 43-44)

"Therefore, the bacosides are likely to undergo transformations in vivo to remove the sugar units as well as other biotransformations, that result in metabolites that may mediate the memory enhancing and cognitive activities." (Ramasamy et al. 2015: 10) - "Thus, it is conceivable that the bacoside constituent present in BM extracts may be metabolized to active forms before exerting their pharmacological activities." (Das et al. 2016: 1799)

This appears to differ from the findings reported by Liu et al. (20130. They demonstrated using middle cerebral artery occlusion reperfusion model rats that the protective effects of bacopaside I on ischemia-induced brain damage were mediated by the suppression of oxidative stress including radical scavenging. The reason(s) for this conflict between our results and their findings currently remains unclear. (Le et al. 2015: 44)

I really wish I had recorded which one of these sources said something to the effect that oxidative stress and free radical scavenging is a fad explanation.

However, in our study, the blockade of ERK by U0126 had no effect on the protective effects of bacopaside I. Therefore, a speculative explanation is that the neuroprotective effects of bacopaside I on ischemic hippocampal cell damage may be mediated by PKC_ε signaling via the modulation of mK_ATP channels. This idea seems to agree with the findings by Liu et al. (2013) that the protective effects of bacopaside I on ischemia-induced brain damage were partly mediated by improvement of brain energy metabolism. (Le et al. 2015: 45)

Nifty. Will keep a watchful eye on ATP from now on.

Khilwani, Barkha; Amanpreet Kaur, Ritika Ranjan and Anil Kumar 2016. Direct somatic embryogenesis and encapsulation of somatic embryos for in vitro conservation of Bacopa monnieri (L.) Wettst. Plant Cell Tissue and Organ Culture 127(2): 433-442. DOI: 10.1007/s11240-016-1067-5

Bacopa monnieri (L.) Wettst., family Scrophulariaceae, is a perenial [sic] herb known for its pharmaceutical properties. Because of its memory related benifits [sic], it is also known as 'Brahmi' or 'Thinking person's herb' (Satyavati et al. 1976). It is widely used for the treatment of mental and neurological disorders (Rastolgi et al. 1994). The extracts of 'Brahmi' are also important in the pharmaceutical industry because of anti-inflammatory, cancerous [sic], oxidative and pyretic properties (Nadkarni 1976). (Khilwani et al. 2016: 433)

As with the early authors who spoke of "memory molecules", this source is not available online. Also, I'm beginning to notice that those who attribute it to the family Plantaginaceae instead of Scrophulariaceae have a higher quality of writing. (The same can probably be said of the -i and -a endings, though I have yet to verify this hunch.)

This enlivening popularization of the herb has dramatically increased extraction from the natural habitat and this herb is now listed in the International Union for Conservation of Nature (IUCN) red list of 1990 of threatened plant species (Govindarajan et al. 2005; Pandey et al. 1993). Therefore, there is an urgent need to take steps for the conservation of this herb to ensure its availability in the future. B. monnieri is placed second on a priority list of the most important medicinal plants (Rajani 2008) and is one among 32 medicinal plant species identified for cultivation and conservation (National Medicinal Plants Board 2004). (Khilwani et al. 2016: 433)

About the third of fourth note like this. Will have to see how the conservation efforts pan out.

In conclusion, direct somatic embryogenesis and shoot bud organogenesis was achieved from leaf explants of B. monnieri and factors affecting somatic embryogenesis were studies. (Khilwani et al. 2016: 441)

Studies they were.

Pei, Jinxin V.; Mohamad Kourghi, Michael L. De Ieso, Ewan M. Campbell, Hilary S. Dorward, Jennifer E. Hardingham and Andrea J. Yool 2016. Differential Inhibition of Water and Ion Channel Activities of Mammalian Aquaporin-1 by Two Structurally Related Bacopaside Compounds Derived from the Medicinal Plant Bacopa monnieri. Molecular Pharmacology< 90(4): 496-507. DOI: 10.1124/mol.116.105882

Aquaporin (AQP) water channels are in the family of major intrinsic proteins found from bacteria to humans and are targets for the discovery of selective pharmacologic modulators. Classes of aquaporins transport water and small uncharged molecules such as glycerol and urea through individual pores located in each subunit. (Pei et al. 2016: 496)

General education portion.

Our study has broadened the panel of AQP modulatory agents by evaluating natural medicinal plants as sources of active compounds. Quantitative swelling assays of mammalian AQP1 and AQP4 channels in the Xenopus expression system, used for screening extracts from a variety of traditional medicinal herbs, have identified Bacopa monnieri as one of several promising sources. Work here tested the hypothesis that chemical constituents of B. monnieri could be identified and characterized as pharmacologic agents that modulate mammalian AQP1 by interacting at domains associated with pore functions. (Pei et al. 2016: 497)

There is something immanently respectable about stumbling upon BM by chance rather than taking it up because of its touted medicinal benefits or, redundancy forbid, its free radical scavenging capability.

Data here show that bacopaside I blocks both the water and ion channel activities of AQP1 but does not alter AQP4 activity, and bacopaside II selectively blocks the AQP1 water channel without impairing the ionic conductance. These results fit well with in silico docking for predicted energies of interaction at a pore-occluding intracellular site. Bacopasides I and II showed the same order of efficacy in blocking migration of AQP1-expressing HT29 colon cancer cells, with minimal effects on SW480 cells that express AQP1 at low levels. (Pei et al. 2016: 497)

Neat. I'm not sure what the significance of this finding is but hopefully the rest of the paper will enlighten.

Ion Channel Conductance of AQP1 Was Inhibited by Bacopaside I but Not by Bacopaside II. (Pei et al. 2016: 500)

Likewise, "bacopaside I exerted more potent neuroprotective effects against OGD-induced neuronal cell damage than bacopaside N2 and a mixture of bacopaside II and bacopasaponin D" (Le et al. 2015: 43). That is, bacopaside I is the active phytochemical, as opposed to bacopaside II, N2, and D.

Bacopaside II Was More Effective Than Bacopaside I in Blocking Migration of AQP1-Expressing Colon Cancer Cells. (Pei et al. 2016: 501)

Huh.

Bacopasides I and II are triterpene glycosides, composed of a hydrophotic pentacyclic terpene backbone (estimated logP value approximately 9; enabling membrane permeability), and three linked polar sugar groups (arabinofuranosyl - glucopyranosyl - arabinopyranose in bacopaside I; and arabinofuranosyl - sulfonyl-glucopyranosyl - glucopyranose in bacopaside II) that appear from in silico modeling to lodge via H-bonds into the water pore entrance of AQP1, with the exception of the sulfonyl group which appears to require an interface with positively charged residues (arginines in the adjacent AQP1 loop D domain). (Pei et al. 2016: 505)

Again, "the main difference observed in chemical structures of bacopaside I and the three other bacosides was a sulfate group on the sugar moiety of bacopaside I" (Le et al. 2015: 43-44).

The identification of bacopasides as novel AQP modulators expands the database of pharmacophore properties of AQP ligands. Bacopasides I and II themselves might not be ideal as drug candidates, exceeding limits of Lipinski's Rule of Five for molecular weight, hydrophobicity, and number of hydrogen bond donors and acceptors - although natural products often show biologic activity as exceptions to the rule (Ganesan 2008). Bacopasides administered in vivo are likely to act as metabolic derivatives as well as intact compounds. More work is needed to define in vivo metabolites of bacopasides and characterize their effects on aquaporins. Nonetheless, bacopasides could serve as lead compounds for the design of small-molecule blockers of aquaporins. (Pei et al. 2016: 505)

"These unfavorable physiochemical traits of the parent bacosides" (Ramasamy et al. 2015: 7) have already been noted.

Block of AQP1 could contribute to the anti-inflammatory benefits of brahmi treatment. [...] Pharmacologic inhibitors of AQP1 channels could be useful for intervention in many conditions, including slowing metastasis in AQP1-positive cancer subtypes. (Pei et al. 2016: 505)

The significance of these findings. Could explain its anti-proliferative activity with regard to metastasis (cf. Mallick et al. 2015).

Thakur, Jay Prakash; Rumana Haider, Dhananjay Kumar Singh, Balagani Sathish Kumar, Prema G. Vasudev, Suaib Luqman, Alok Kalra, Dharmendra Saikia, and Arvind S. Negi 2015. Bioactive isochromenone isolated from Aspergillus fumigatus, endophytic fungus from Bacopa monnieri. Microbiology Research 6(1): 14-18. DOI: 10.4081/mr.2015.5800

Brahmi (Bacopa monnieri) is an important medicinal herb used in Ayurveda system of medicine in India. The herb was described in Charaka Samhita, Susrutu Samhita and Athar-Ved to sharpen intellect and attenuate mental deficits. It is a perennial, creeping herb native to the wetlands of India. Other than India, it is also found in Europe, Asia, Australia, Africa and Americas. It grows well in marshy areas. Traditionally, this herb is mainly prescribed for neurological disorders like epilepsy. Its extract has shown potential cognitive effects. Bacosides are the main bioactive compounds of Brahmi. (Thakur et al. 2015: 14)

Nothing out of the ordinary. Based on the meta-analysis by Kongkeaw et al. (2014).

In conclusion, the present study has described isolation of 6-hydroxy mullein (1) from A. fumigatus hosted in B. monnieri plant. To the best of our knowledge this is the first report of this metabolite from this fungus. Our study suggests that not only plants but some other fungy may also be a good source of antioxidant compounds and A. fumigatus is one such potential candidate presenting a better scope for production [of] bioactive compounds. (Thakur et al. 2015: 17)

Very intredasting.

Bansal, Mahima; M. Sudhakara Reddy and Anil Kumar 2016. Seasonal variations in harvest index and bacoside A contents amongst accessions of Bacopa monnieri (L.) Wettst. collected from wild populations. Physiology and Molecular Biology of Plants 22(3): 407-413. DOI: 10.1007/s12298-016-0366-y

The maximum dry weight of plant (biomass 1.64 g) and bacoside A levels (6.82 mg/plant) were recorded in accession BM1. Harvestable biomass was highest during summer in accessions BM1 and BM7 (FW 4.2 g/plant), whereas bacoside A levels were also highest during summer and in accession BM1 (6.82 mg/plant). The lowest bacoside A level (0.06 mg/plant) was recorded in accession BM14 during winter. (Bansal, Reddy & Kumar 2016: 407)

That's a pretty significant variation between seasons. Could this illuminate the native function of bacosides in the plant?

Bacopa monnieri (L.) Wettst. family Scrophulariacea (common name 'Brahmi'), is an important source of bacosides, which possess a legendary reputation as a memory vitalizer with a proven nootropic action (Anonymous 1988). It has been a focus of many studies due to its medicinal uses (Russo & Borrelli 2005). Brahmi-based herbal drugs like 'Mentat', 'Memory Plus' and 'Memory Perfect' rich in bacoside A are gaining popularity in both developed and developing countries (Pase et al. 2012). Recent studies also reported anti-cancer activity of the extracts of B. monnieri (Sharma et al. 2012). (Bansal, Reddy & Kumar 2016: 407)

Isn't BM, to the best of our knowledge, the only source of bacosides? Legendary reputation implies that there are some legends (stories, narratives) related to it, which I'd be very interested in if there were.

These populations were evaluated from the samples collected from different regions thus, the observed results could also be due to environmental and edaphic factors. (Bansal, Reddy & Kumar 2016: 408)

Define:edaphic - "of, produced by, or influenced by the soil."

Further, Soni et al. (2015) reported that secondary metabolites accumulate during the growing seasons in medicinal plants, which is also in line with the present observations in B. monnieri accessions. Moreover, in this study accession BM1 collected from Kolkata where the average temperature is higher) recorded maximum levels of bacoside A, whereas accession BM14 recorded lowest level of bacoside A. This accession was collected from Jogindernagar, Himachal Pradesh (1500 m amsl) where temperature conditions prevail and the average temperature is lower. These results suggest that accessions collected from the warmer region have a higher potential of bacoside A production as compared to accession collected from the colder area. (Bansal, Reddy & Kumar 2016: 410)

How does this mesh with the datum that "These secondary metabolites are not directly related to the physiological growth of plants but help in the plant's longevity" (Leonard et al. 2017: 2)?

Karataş, Mehmet; Muhammad Aasim and Muraz Dazkirli 2016. Influence of light-emitting diodes and benzylaminopurin on adventitious shoot regeneration of water hyssop (Bacopa monnieri (L.) Pennell) in vitro. Archives of Biological Sciences 68(3): 501-508. DOI: 10.2298/abs150803039k

Water hyssop (Bacopa monnier (L.) Pennell) or Brahmi is a well-known Indian plant grown in damp and marshy areas. It is on of the most important medicinal plants, which contains medicinally important alkaloids, saponins, flavonoids and bacosides, used as cardiac or brain tonic, for treating anxiety and epileptic disorders, for their diuretic, analgesic, anti-inflammatory and antipyretic activities, treatment of snakebites, spleen enlargement, rheumatism, ringworm, leprosy, eczema, asthma, irritable bowel syndrome, gastric ulcers and bronchitis. (Karataş, Aasim & Dazkirli 2016: 501)

Some items in some lists such as this are somewhat "out there", i.e. wound healing activity (Gupta et al. 2017c: 1-2), unsupported by any papers I've come across.

Plant tissue culture provides an alternative way to propagate plants under controlled conditions and also makes it possible to alter metabolite concentrations using modern biotechnological techniques such as genetic transformation, modifying growth media or culture conditions. Lighting systems or photoperiod are one of the major components of successful regeneration protocols in vitro, also providing an opportunity to alter secondary metabolite concentrations in plants. Light-emitting diodes (LEDs) offer an alternative lighting system available in different colors. (Karataş, Aasim & Dazkirli 2016: 501)

Whoda thunk those lights meatheads attach under their cars can be used for growing plants? Is light what plants crave?

LED type and the combinations of R[ed] and B[lue] lights exhibited statistically significant differences on the number of shoots per explant and shoot length. [...] The W[hite] LED lighting system was more efficient for regenerating the maximum number of shoots per explant compared to the R:B LEDs, irrespective of explant type. (Karataş, Aasim & Dazkirli 2016: 504)

Sad. Red and blue LEDs are undoubtedly much more aesthetically pleasing.

Explants such as shoot tips, internodes, meristematic nodes and leaves, are commonly used for in vitro regeneration of water hyssop. Among these explants, the leaf explant is the most potent explant. (Karataş, Aasim & Dazkirli 2016: 505)

Noted by many before, recording it here because it sounds interesting enough on its own.

Results further confirmed the importance of cutting the leaf into an upper and lower half, which reached twice the number of shoots compared to the full leaf, irrespective of BA concentration. (Karataş, Aasim & Dazkirli 2016: 506)

Might be useful should I ever grow the plant myself (doubtful).

Dogan, M.; Hasan Akgul; O. G. Inan and H. Zeren 2015. Determination of cadmium accumulation capabilities of aquatic macrophytes Ceratophyllum demersum, Bacopa monnieri and Rotala rotundifolia. Iranian Journal of Fisheries Sciences 14(4): 1010-1017.

Among heavy metals, Cd is a heavy metal with no known essential biological functions in higher plants. Although it is naturally released into the environment, substantial sources of Cd in the environment are human activities. Such activities include power stations, heating systems, metal working industries, urban traffic or phosphate-containing fertilizers. Cadmium is widely used in electroplatinig [sic], pigments, plastic stabilizers, and Ni-Cd batteries. Because of its high solubility in water and high toxicity, it is recognized as a highly significant environmental pollutant. (Dogan et al. 2015: 1011)

General education portion.

Several of the submerged, emergent and free-floating aquatic macrophytes are reported to accumulate heavy metals in natural waters as well as after exposure to wastewaters. [...] B. monnieri L. grows very fast with its creeping stem in wetlands. Heavy metal accumulation capabilities of B. monnieri have been reported in many studies (Ali et al. 2001; Singh et al. 2006). (Dogan et al. 2015: 1011)

Didn't know it grew fast. Did know about heavy metal accumulation (cf. Jain et al. 2017; Mishra et al. 2016).

Considering individual macrophyte applications, the highest Cd accumulation was observed in R. rotundifolia tissues. In contrast, the lowest Cd accumulations were determined in B. monnieri tissues. (Dogan et al. 2015: 1012)

Noice.

Submerged macrophytes like C. demersum and R. rodundifolia up take metals directly from the water column. Thus, these macrophytes have higher metal accumulation capabilities than B. monnieri, an emersed macrophyte. (Dogan et al. 2015: 1015)

Not all aquatic plants are alike.

Taznin, Inin; Mohsina Mukti and Mohammed Rahmatullah 2015. Bacopa monnieri: An evaluation of antihyperglycemic and antinociceptive potential of methanolic extract of whole plants. Pakistan Journal of Pharmaceutical Sciences 28(6): 2135-2139. PMID: 26639482

Bacopa monnieri (L.) Penn. (Family: Scrophulariaceae) is a perennial herb found growing in the wild in wetlands of Bangladesh. The plant is known in Bengali as 'brahmi shak', and in English as watter hyssop. Whole plants are used by folk medicinal practitioners primarily for improvement in memory and to prevent memory loss, but also used to lower high sugar levels in diabetic patients and to alleviate pain (Ghost et al. 2008; Subhan et al. 2010). The plant has also uses in the Ayurvedic system of traditional medicine to prevent memory loss and to improve cognitive functions. A recent study has shown the efficacy of the plant in schizophrenia (Sharkar et al. 2012). (Taznin, Mukti & Rahmatullah 2015: 2135)

Companion to "Neer-Brahmi" in Tamil and "Jalabrahmi" in Kannada.

Wound healing activity has been reported for a compound, namely bacoside-A, isolated from the plant (Sharath et al. 2010). (Taznin, Mukti & Rahmatullah 2015: 2135)

Dis gon be gud.

The analgesic effect of bacopasides found in the plant has been reviewed (Rauf et al. 2013). (Taznin, Mukti & Rahmatullah 2015: 2135)

Also something I'd like to know more about.

Isolated phytochemicals reported from the plant include cucrubitacins, namely bacobitacin A-D, and phenylethanoid glycosides, namely monnieraside I and III along with plantioside B (Bhandari et al. 2007); triterpene glycosides and their analogues, namely bacopasides VI-VIII, bacopasides I and II, and bacopasaponin C, the latter three compounds having antidepressant activities (Zhou et al. 2007); bacosterol glycoside (Bhandari et al. 2006); and triterpenoid glycosides and saponins (Sivaramakrishna et al. 2005). (Taznin, Mukti & Rahmatullah 2015: 2136)

Some of these haven't been even mentioned in any of the recent papers I've read lately.

We had been investigating the antihyperglycemic and antinocineptic potential of medicinal plants used in folk medicinal system of Bangladesh to lower high blood sugar levels and for alleviation of pain for several years. Such evaluation leads not only to scientific validation of folk medicinal uses, but also serves as a pointer for further scientific studies leading towards isolation and identification of the responsible phytochemical constituent(s), which in turn can lead to discovery of potentially more efficacious drugs. (Taznin, Mukti & Rahmatullah 2015: 2136)

Antinocineptive, pharmacological term for a drug that inhibits nociception, the sensation of pain.

Whole plants of B. monnieri were collected in February 2013 from Pabna district, Bangladesh. (Taznin, Mukti & Rahmatullah 2015: 2136)

Right when the plant has the lowest levels of bacoside A content (cf. Bansal, Reddy & Kumar 2016: 407). And of course they didn't even measure the bacoside content. Those poor Swiss albino mice.

The results show that even at an extract dose of 50mg per kg body weight, the extract attenuated the number of gastric constrictions better than that of aspirin. (Taznin, Mukti & Rahmatullah 2015: 2137)

Sure sounds like they were just drunk from your crude methanol extract.

Bacopasides, isolated from the plant has been reported to be an emerging class of therapeutics for management of particular chronic pains (Rauf et al. 2013). Bacosine has also been reported for demonstrating analgesic effects (Vohora et al. 1997). (Taznin, Mukti & Rahmatullah 2015: 2138)

Inaccessible source for the latter citation. The abstract for Vohora et al. (1997) says that the analgesic effects of bacosine were moderate and opioidergic in nature. Not very promising.

Sharma, Munish; Rajinder Gupta, Ravi Kant Khajuria Sharada Mallubhotla and Ashok Ahuja 2015a. Bacoside biosynthesis during in vitro shoot multiplication in Bacopa monnieri (L.) Wettst. grown in Growtek and air lift bioreactor. Indian Journal of Biotechnology 14(4): 547-551.

Growing demand for Bacopa monnieri (L.) Wettst. (Family: Scrophulariaceae), commonly known as Brahmi, and the beneficial effects of its constituents (bacosides) encouraged research into developing efficient methods for controlled cultivation by in vitro approaches. In vitro shoot cultures of B. monnieri provide a potential alternative to mass harvesting of plants for the purpose of obtaining bacosides. (Sharma et al. 2015a: 547)

The verified medicinal effects are probably the cause for such a great amount of biotechnological studies of cultivating the plant. BM is touted as the most-researched nootropic plant, and the micropropagation studies certainly bolster that claim.

Growtek culture is practically a closed system, in which gas exchange is slow and, as the culture grows, O₂ content diminishes and CO₂ builds up, which is probably responsible for the lower growth rate. In contrast, ALB system supplied with a constant flow of air, which can keep the dissolved oxygen level high, contributed to a significant increase in the shoot regeneration rate. Higher shoot biomass of B. monnieri has been recently reported in Growtek bioreactior when it was supplied with aeration. [...] Higher bacoside content indicates that the accumulation of bacosides is associated with aeration provided in the air lift bioreactor system. It is well reported that high aeration improves oxygen transfer, a process that improves growth and secondary metabolite production. (Sharma et al. 2015a: 550)

Turns out, air is also what the plants crave.

The maximum content was recorded in shoot biomass cultured in ALB system, which reached 10.15 mg/g DW as compared to 6.08 mg/g DW recorded for Growtek® culture, both of which were higher compared to the shake flask culture (5.78 mg/g DW). (Sharma et al. 2015a: 550)

Impressive.

It is possible that the forced aeration of the air lift bioreactor has contributed to the reduction in sugar usage by the explants due to increased photosynthetic capacity. (Sharma et al. 2015a: 551)

Actually interesting: if plants "suffocate", their ability to produce nutrients on their own (photosynthesis) diminishes and they'll resolt to sugars in the medium.

Packyanathan, Jerusha Santa; R. Gayathri and V. Vishnupriya 2016. Preliminary phytochemical analysis and cytotoxicity potential of Bacopa monnieri on oral cancer cell lines. International Journal of Pharmaceutical Sciences Review and Research 39(1): 4-8.

Medicinal plants have been identified and used throughout human history. In India, the Ayurveda medicinal system is based on herbs. Plants have the ability to synthesize a wide variety of chemical compounds that are used to perform important biological functions, and to defend the body. Ethnobotany, the study of traditional human uses of plants, is recognized as an effective way to discover future medicines. Some plants contain phytochemicals that have positive effects on the body. Chemical compounds in plants mediate their effects on the human body through processes identical to conventional drugs. This enables herbal medicines to have beneficial pharmacology. (Packyanathan, Gayathri & Vishnupriya 2016: 4)

With the ethnobotanical portion I agree, and await the male birth control pill from Indonesia. With identical processes I'm not on board since not one study I've read thus far has indicated that BM mimicks the effects of any known drug.

Bacopa monnieri is an antioxidant. Bacopa monnieri displays in vitro antioxidant and cell-protective effects (Russo & Borrelli 2005). Bacopa monnieri interacts with the dopamine and serotonergic systems, but its main mechanism concerns promoting neuron communication. It does this by enhancing the rate at which the nervous system can communicate by increasing the growth of nerve endings, also called dendrites. (Packyanathan, Gayathri & Vishnupriya 2016: 4)

That's a bold statement, probably unsupported by sources cited here (Russo & Borrelli 2005 will be included in the next cycle of papers, the one after that at the latest). By what I've read thus far I can't say that it promotes neuron communication. What there is ample support for is that it "improvement of brain energy metabolism" (Le et al. 2015: 45), which might amount to the same, yet is perhaps not as glamorous.

However, an emerging prospect for treatment of cancer is the use of herbs like Bacopa monnieri due to their phytochemical and cytotoxic properties against cancer. Organic extracts of B9_Pink (Fusarium oxysporum) and B19 (Fomitopsis sp.) are found to possess potent cytotoxic and antimicrobial properties, highlighting their possible potential for use in the development of anti-concer drugs, which needs to be further studied [Targeted Cancer Therapies Fact Sheet - National Cancer Institute] (Packyanathan, Gayathri & Vishnupriya 2016: 4)

Wikipedia says nada, and online source seems to have removed the portion, probably deeming it ineffective.

The "phyto-" of the word phytochemicals is derived from the Greek word 'Phyto', which means plant. Therefore, phytochemicals are plant chemicals. (Packyanathan, Gayathri & Vishnupriya 2016: 4)

Contrary to expectation, Captain Obvious is not attributed as an author of this paper.

Tannins which are a group of phenolic compounds that are known antimutagenic property and can act against cancer cells (Chung et al. 1998). (Packyanathan, Gayathri & Vishnupriya 2016: 7)

Got at least one interesting citation out of this paper. Tannins appear frequently in phytochemical screenings of BM but not much else is said about these phytochemicals.

Shinomol, George K.; M.M. Srinivas Bharath and Muralidhara 2012. Pretreatment with Bacopa monnieri extract offsets 3-nitropropionic acid induced mitochondrial oxidative stress and dysfunctions in the striatum of prepubertal mouse brain. Canadian Journal of Physiology & Pharmacology 90(5): 595-606. DOI: 10.1139/Y2012-030

Bacopa monnieri L. (Brahmi; BM) is a herb that has been extensively used for centuries in the Ayurvedic system of medicine as a brain tonic and to promote longevity (Padma 2005: Singh et al. 2008). Traditionally, it was used as a brain tonic to enhance memory development, learning, and concentration and to provide relief to patients with anxiety or epileptic disorders (Chopra 1958; Gohil & Patel 2010; Shimonol et al. 2011a). (Shinomol, Bharath & Muralidhara 2012: 596)

I've noticed sparse mentions of longevity but not as much mentions of concentration. Right off the bat the authors should be commended for including DOI's and PMID's with references. This is only the second paper thus far that is in the 21st century like that.

The neuroprotective- and cognitive-enhancing effects of BM extracs are thought to be due to several mechanisms such as chelation of metal ions, scavenging of free radicals, and enhanced antioxidative defense enzymes (Bhattacharya et al. 2000). Further, the antistress activity of BM in experimental animals is attributed to its propensity to modulate Hsp70 [Heat Shock Protein] expression, cytochrome P450 levels, activity of superoxide dismutase (Chowdhuri et al. 2002), enhanced kinase activity, neuronal synthesis coupled with restoration of synaptic activity, and nerve impulse transmission (Kishore & Singh 2005). (Shinomol, Bharath & Muralidhara 2012: 596)

Others have mentioned that it "chelates iron. (Chaudhari et al. 2017: 111) and "metal chelating" (Phulara et al. 2015: 414), and "The role of bacoside A against chronic sigarette smoking-induced Hsp70 expression and apoptosis in rat brain cerebral cortex" (Prasad et al. 2008: 105). Restoration of synaptic activity is outside of my reach because Kishore & Singh (2005) is not available online.

Recently, we showed that BM ethanolic extract (BME) modulates the endogenous levels of oxidative markers in brain regions of prepubertal mice (Shimonol & Muralidhara 2011). Previously, we demonstrated the neuroprotective action of BM against selected neurotoxicants, viz. rotenone and paraquat, in the Drosaphila model (Hosamani & Muralidhara 2009, 2010). Hence we hypothesized that prophylaxis with BME is likely to render the brain less susceptible to neurotoxicant-induced, oxidative stress mediated neuronal dysfunctions. (Shinomol, Bharath & Muralidhara 2012: 596)

"Prophylactic" is immensely suitable word for it. I'd also call BM, after this effect, the great normalizer, since it seems to protect the CNS against a host of toxicants.

They were acclimatized for 1 week prior to the start of the experiment and were maintained on a powdered diet and tap water ad libitum. (Shinomol, Bharath & Muralidhara 2012: 596)

Something to think about for that short story: should the "standard human feed" be protein powder instead of fast food?

The experiments were conducted in strict accordance with approved guidelines by the institution's animal ethical committee regulated by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Social justice and Empowerment, Government of India, India. (Shinomol, Bharath & Muralidhara 2012: 596)

Good name. The Soviety ministry of humour would approve.

Significant increases in the endogenous levels of GSH [glutathione] (34%), total thiols (28%), and nonprotein thiols (27%) were evident among mice receiving BME prophylaxis alone. Administration of 3-NPA [a well-known fungar mitochondrial toxin] to control mice caused a significant depletion in the levels of GSH (31%), total thiols (37%), and nonprotein thiols (48%) in striatal mitochondria. Interestingly, among mice given BME prophylaxis, 3-NPA did not diminish the levels of GSH, total thiols, and nonprotein thiols, suggesting complete protection. Further, a marginal decrease was evident in the levels of oxidized glutathione among mice receiving BME prophylaxis alone. (Shinomol, Bharath & Muralidhara 2012: 599)

Thus, the renowned antioxidant properties of BM stems partly from its ability to enforce endogenous antioxidant mechanisms. Depletion explained elsewhere: "The ROS generated during glycation and glyoxidation are able to oxidize side chains of amino acid residues in protein to form carbonyl derivatives and also diminish an oxidative defense of protein by decreasing thiol groups (Balu et al. 2005)" (Kishore, Kaur & Singh 2016: 1539).

Mahender, Aileni; Bulle Mallesham, Kota Srinivas, Gadidasu Kranthi Kumar, Kokkirala Venugopal Rao, Yarra Rajesh, Peng Zhang and Abbagani Sadanandam 2012. A rapid and efficient method for in vitro shoot organogenesis and production of transgenic Bacopa monnieri L. mediated by Agrobacterium tumefaciens. In Vitro Cellular & Developmental Biology - Plant 48(2): 153-159. DOI: 10.1007/s11627-011-9421-0

Indian medicine folklore purports that certain herbs can be used as traditional brain or nerve tonics. One of the most popular is Bacopa monnieri L. (Scrophulariaceae), commonly called Brahmi, a small, amphibious plant growing in marshy areas throughout the Indian subcontinent. Brahmi is also known as "Medhya Rasayana" in Ayurveda as it has been reported to increase mental clarity and brain-stimulating activities (Bhattacharya & Ghosel 1998). It also possesses properties to protect against inflammation, epilepsy, insanity, cancer as well as offering analgesic, antipyretic, and antioxidant activities (Jain et al. 1994; Elangovan et al. 1995; Tripathi et al. 1996; Vohora et al. 1997). (Mahender et al. 2012: 153)

Purporting means falsely appearing to do something. The statement is correct insofar as similar claims are indeed found for other plants as well. On that very same page of Tadarānanda's Materia Medica of Ayurveda, "Vacā (Acorus calamus Linn.)" also "promotes longevity, memory and intellect".

Bacopa extract has anxiolytic, cognition-enhancing (Bhattacharya & Ghosal 1998), relaxing (Dar & Channa 1997), anxiolytic (Mukherjee & Dey 1966), and immuno-modulator activities (Dahanukar & Thatte 1997). (Mahender et al. 2012: 153)

This 2012 paper sure has a lot of old sources.

The natural regeneration of this herb is hampered due to short viability (2 mo) of seeds, frequent death of seedlings at a two-leaf stafe, and strict habitat requirements for marshy areas. (Mahender et al. 2012: 154)

In this light the numerous recent biotechnological studies seem more than warranted and the 140 day viability of synthetic seeds (cf. Khilwani et al. 2016) very impressive.

Siddique, Yasir Hasan; Syed Faiz Mujtaba, Mohammad Faisal, Smita Jyoti and Falaq Naz 2014. The effect of Bacopa monnieri leaf extract on dietary supplementation in transgenic Drosophila model of Parkinson's disease. European Journal of Integrative Medicine 6(5): 571-580. DOI: 10.1016/j.eujim.2014.05.007

Bacopa monnieri has been reported to enhance memory, cognitive properties and life span in the traditional Ayurvedic medicinal system of India (Bhattacharya, Kumar & Ghosal 199). (Siddique et al. 2014: 571)

Cited paper ["Effect of Bacopa monnieri on animal models of Alzheimer’s disease and perturbed central cholinergic markers of cognition in rats"] not found online. (A study from 2 of 3 cited authors from the previous year will appear in the next cycle, cf. Bhattacharya & Ghosal 1998.)

Parkinson's disease (PD) is a neurodegenerative syndrome, characterized by the loss of dopaminergic neurons in the substantia nigra and in the formation of filamentous intraneuronal inclusions known as Lewy bodies (Feany & Bender 2000). (Siddique et al. 2014: 571)

Lewy bodies "are abnormal aggregates of protein that develop inside nerve cells in Parkinson's disease (PD), Lewy body dementia, and some other disorders. They are identified under the microscope when histology is performed on the brain."

The flies were cultured on standard Drosophila food containing agar, corn meal, sugar and yeast at 25 °C (24 ± 1). [...] The climbing assay was performed as described by Pendleton et al. (2002). Ten male flies were placed in an empty class vial (10.5 cm × 2.5 cm). A horizontal line was drawn 8 cm above the bottom of the vial. After the flies had acclimatized for 10 min at room temperature, controls and treated groups were assayed at random, to a total of 10 attempts for each. [...] Brain homogenate was prepared in Tris-HCl and centrifuged at 3000 × g for 20 min and subsequently the supernatant was collected. (Siddique et al. 2014: 572)

Recording these tidbits for that short story, possibly imagining large aliens a la Fantastic Planet making batches of human subjects climb something. Still haven't figured out what the "standard human food" should be, but it should be artificially kept at some awkward temperature.

The treatment of PD flies with B. monnieri leaf extract showed a delay in the loss of climbing ability, activity pattern, reduced oxidative stress and apoptosis in the brains of PD model flies. Oxidative stress is considered to be one of the important factors during the progression of PD (Butterfield & Kanski 2001; Giasson et al. 2002). Free radical scavengers have been reported to reduce the rate of progression of PD (Abbott et al. 1992). The denegerating neurons also produce endogenous toxins [|] (hydrogen peroxide) and other reactive oxygen species that may further damage normal neurons (Giasson et al. 2002). (Siddique et al. 2014: 575-576)

Interesting enough: once degenerating, it produces further damaging substances.

Bacoside, a constituent of B. monnieri, has been reported to repair damaged neurons by enhancing the kinase activity (Tripathi et al. 2011). (Siddique et al. 2014: 576)

Would like to learn more but cited source once again unavailable.

The studies carried out on dietary supplementation of flavanoids rich plants have also shown improvement in cognition functions possibly by protecting vulnerable neurons or by enhancing teh regeneration of neurons (Vazour et al. 2008). Recent findings have suggested that any plant extract rich in antioxidants may have a remodeling effect on the nature of α-synuclein fibrils converting into non-toxic small amorphous aggregates (Bieschke et al. 2010). The accumulation of free radicals and consequent neurodegeneration in the specific brain regions are the causal factors for various neurodegenerative diseases. (Siddique et al. 2014: 578)

Someone please communicate this to the researchers (Tanwar et al.) who "add value" to chicken nugget vacuum packaging with BM when literally any other non-endangered plant with high antioxidant content would do.

A traditional medicinal approach relies on centuries of experience using plant extract of various plants as a whole. [...] Plants represent a major source of biologically active molecules and to date only a small fraction of plants with potential medicinal activity have been explored. Nations such as India and China are rich in traditional knowledge of medicinal plants which can be exploited for research and drug development by pharmaceutical companies for various conditions (Rao et al. 2013 [Online]). (Siddique et al. 2014: 579)

Phraseology for framing the pharmaceutical turn to traditional medicines.

Hussain, K. and Nabeesa Salim 2012. Bioaccumulation Pattern of Mercury in Bacopa monnieri (L.) Pennell. Journal of Stress Physiology & Biochemistry 8(2): 10-21.

Plants growing/cultivated in soil contaminated with heavy metals like mercury are under toxicity stress. Nevertheless, heavy metal ions are absorbed by roots and translocated to the entire plant body and the pattern and the gravity of absorption and translocation depend on the chemistry of the metal, habit, habitat and genetic make up of the plant (Pilon-Smiths 2005). Many plants are hyperaccumulators [that] can accumulate unusually high content of mercury from the environment in the root system and translocate the metal to the aerial parts and most of these are recommended for phytoremediation techniques (Pilon-Smiths 2005). (Hussain & Salim 2012: 11)

General education portion.

In addition, a number of marshy, aquatic or submerged herbaceous plants such as Hydrilla verticillata and Bacopa monnieri have received attention for their role as biological detoxification systems for phytoremediation of Hg, Cd, Cr, Cu, Fe, and Mn contamination (Sinha et al. 1993; 1997; Sinha 1999; Sinha & Pandey 2003; Sinha et al 2003; Askari et al. 2007). (Hussain & Salim 2012: 12)

Another study found that BM is not a hyperaccumulator exactly because it is an emersed macrophyte and not a submersed one (cf. Dogan et al. 2015: 1015).

Bacopa monnieri has been used in Ayurvedic systems of medicine and traditionally it is used as a 'brain tonic' to enhance memory development (Nair 1978). According to Wohlmut (2001), Nathan et al. (2001) and Stough et al. (2001) Bacopa monnieri is an Ayurvedic herb and currently enjoying the popularity as 'brain herb'. Many products derived from B. monnieri are available in nutraceutical market with content of bacoside A and B (Deepak & Amit 2004). (Hussain & Salim 2012: 12)

Just collecting variations on the theme of "memory enhancer". "Brain herb" likewise goes well with "Thinking person's herb" and "memory molecules". The point about the nutraceutical market is poignant, as there are indeed many preparations to choose from.

In addition to the well-established multipurpose medicinal use, Bacopa monnieri has been recommended for phytoremediation due to the hyperaccumulation potential (Sinha et al. 1996; Sinha 1999; Yadav, Sukla & Rai 2005). In this contet the fate of the plant for medicinal uses should be determined and considered as part of risk assessment because many Ayurvedic preparations containing B. monnieri are available in the market and are profusely consumed by humans. Therefore, the dual uses or qualities of B. monnieri i.e. phytocemediant on the other hand and medicinal on the other do pose a threat to mankind. (Hussain & Salim 2012: 12)

Surely not mankind as a whole? Only those people consuming the plant material that is not treated with ethanol to remove the pollutants.

Since the entire plant is used for medicinal purpose, accumulation of otxic metals in root, stemp and leaf may highlight the gravity of health hazard due to the entry of the toxic metals to human body. (Hussain & Salim 2012: 12)

This is the umpteenth mention of of whole plant being used. But should it?

Pilon-Smiths (2005) opines that the bulk flow of the metal ions from root to shoot and leaf is driven by transpiration which creates negative pressure potential in the xylem that pulls up water and solutes. (Hussain & Salim 2012: 17)

Having flashbacks to our biosemiotics professor K. K. explaining this and my eyes glazing over at the time.

Accumulation of Hg in Bacopa monnieri cultivated in nutrient solution is found to be dependent on the pH of the growth medium. Acidic pH encourages Hg accumulation while alkaline pH results in reduced accumulation. These qualities are beneficial for the two [dual?] economic importance of Bacopa monnieri in such a way that for phytoremediation technology reduction of pH can be done by adding NH₄Cl, which acts also as nutrient for profused growth (Sharif & Khan 2009). On the other hand alkaline pH can be maintained by liming before harvesting for medicinal purpose because accumulation of Hg significantly reduced at high pH. (Hussain & Salim 2012: 18)

Interesting enough for potential growers.

The loss of the metal from the shoot system by phytovolarilization results in the lowering of the ration and hence Bacopa monnieri can not be included under hyperaccumulators of Hg. (Hussain & Salim 2012: 19)

Apparently BM does not straight up accumulate it but lets it into the air via leaves.

Kumar, Navneet; L. G. Abichandani, Vijay Thawani, K. J. Gharpure, M. U. R. Naidu and Venkat G. Ramana 2016. Efficacy of Standardized Extract of Bacopa monnieri (Bacognize®) on Cognitive Functions of Medical Students: A Six-Week, Randomized Placebo-Controlled Trial. Evidence-Based Complementary and Alternative Medicine Article 4103423. DOI: 10.1155/2016/4103423

Bacopa monnieri (Linn.) Pennell, family Scrophulariaceae (Sharma, Yelne & Dennis 2000 [Database on Medicinal Plants Used in Ayurveda, pp. 93-101]), is an indigineous plant, found throughout India, Nepal, Sri Lanka, China, Taiwan, Vietnam and Florida, Hawaii, and some other southern states of USA. It is also known as "Brahmi." Its description in Indian scriptures dates back to 5000 BC. It has been used in Ayurveda since 500 AD as "Medhya Rasayana" (Sharma 1998 [Dravyaguna-Vijñāna]) for treatment of anxiety, poor memory, epilepsy (Badmaev 1998 [Bacopin (Bacopa monnieri): A Momery Enhancer from Ayurveda}, improvement of cognitive processes, comprehension, memory, and recall (Mukherjee & Dey 1966). It is currently promoted as a brain tonic and many formulations are available. (Kumar et al. 2016: 1)

What scriptures, though? Finally someone noticed that Florida has mapped its distribution of the plant (online map available).

Bacopa extract has been shown to possess dose dependent free radical scavenging capacity and protective effect on DNA cleavage (Russo et al. 2003). Its antioxidant property, which is about half potent to that of vitamin E on weight basis (Tripathi et al. 1996), is thought to be responsible for its antistress, immunomodulatory, cognition facilitatory, anti-inflammatory, and antiageing effects (Bhattacharya & Ghosal 1998; Singh & Dhawan 1982; Singh et al. 1988; Dar & Channa 1997; Elangovan et al. 1995; Dahanukar & Thatte 1997; Jain et al. 1994). Its antilipid peroxidation property is credited to the [|] memory enhancing action and it has been recommended for lw dose long-term therapy rather than single high dose administration (Tripathi et al. 1996). (Kumar et al. 2016: 1-2)

Immunomodulatory and anti-inflammatory mechanisms are different? Shouldn't it be high dose long-term therapy?

Animal studies have shown that it has anxiolytic, cognition enhancing, relaxing, bronchodilatory, antioxidant, anticancer, antidepressant, immunomodulatory, and anti-inflammatory effects. Its anxiolytic activity was comparable to benzodiazepine but did not result in any significant memory deficit. It improved acquisition, retention, and retrieval of learned tasks. Mouse model shows that its antidepressant properties which may be due to its effect on serotonergic and noradrenergic nervous system (Girish, Oommen & Vishnu 2016). (Kumar et al. 2016: 2)

Important points of comparison. Noradretarite = norepinephrine.

Trial with a Composite Indian Herbal Preparation (CIHP), which amongst other constituents contained Brahmi, has been shown to be beneficial for soldiers serving at high altitudes and cold areas and in low intensity confluct situations. It improved their physical and mental efficacy (Singh 2004 [A Herbal Stress Buster for Soldiers]). (Kumar et al. 2016: 2)

Very interesting stuff, though source out of reach.

Bacoside A and B improve the transmission of impulses between the neurons. Bacosides regenerate synapses and repair damaged neurons, thereby making it easier to learn and remember new information. Brahmi increases brain serotonin, a neurotransmitter promoting relaxation (Rastogi & Kulshreshtha 1998). Bacosides A and B influence cholinergic system (Bhattacharya et al. 2000). (Kumar et al. 2016: 2)

Bold claims. I'll have to see if the next cycle, consisting of early papers, backs this up.

The potent antioxidant property exerted by Brahmi has been shown to be due to metal chelation at the initiation level and also as a chain breaker (Tripathi et al. 1996). The mechanisms resembles that of EDTA and vitamin E. Standardized extract of Bacopa monnieri induced a dose related increase in superoxide dismutase, catalase, and glutathione peroxidase levels in rat prefrontal cortex, striatum, and hippocampus (Bhattacharya et al. 2000). (Kumar et al. 2016: 2)

Metal chelation is also mentioned as removing excess of toxic metals from the bloodstream (Muszyńska et al. 2016: 2443).

Single dose of 300 mg of standardized extract of Bacopa monniera failed to show any effects on normal healthy adults (Sharma et al. 1987). Follow-up study with higher single dose in a double blind, placebo-controlled trial showed improved and sustained cognitive performance (Nathan et al. 2001). (Kumar et al. 2016: 2)

Would a single bout of exercise improve fitness?

Chronic effects of Bacopa when assessed on memory functions in 76 adults from 40 to 60 years' age group, for three months, showed significant effects on retention of new information (Roodenrys et al. 2002). (Kumar et al. 2016: 2)

You can say that again.

Since none has been attempted on a select, exclusive group of participants with high intellectual level, like medical students, we planned this study to see whether the drug is effective in improving cognitive functions in medical students after 6 weeks of treatment. [↩] Our rationale behind this exclusive sample was that medical physicians are known to have a very high intellectual level (Hauser 2002 [Meritocracy, Cognitive Ability, and the Sources of Occupational Success]). So we wanted to see if Bacopa monnieri can improve cognition in the group of medical students with already high cognitive functions. (Kumar et al. 2016: 2)

Exactly my thoughts in 2014 when finding out about BM on reddit's nootropic community, where already intelligent and high-functioning people look for substances that'll give them a further edge.

The exclusion criteria were

1. consumption of any memory improving medicines, alcohol, tobacco, or any other Central Nervous System (CNS) acting medicines,

(Kumar et al. 2016: 2)

Ironically, noot-users would automatically be excluded from such studies.

[...]

1. using Brahmi in any form, for example, hair oil.

(Kumar et al. 2016: 3)

Only mention, thus far, I've seen of Brahmi as a hair care product.

Digit Span Memory Task. It involves immediate verbal recall of numbers, varying from 6 to 10 digits, and consists of digit span forwards and backwards. Digit span forwards requires recall of the series of numbers in the same order as given. The test measures are closely related to the efficacy of attention (freedom from distractibility). Digit span backwards requires immediate recall of the spoken numbers in the reverse order. Measuring the elements of working memory, it requires both recall and subsequent manipulation of the incoming information. (Kumar et al. 2016: 4)

Negative, but useful, definition of attention. Cf. "flow", the psychological concept.

Paired Associate Task. It consists of 10 predetermined word pairs. Participants are first presented with the pairs before the start of the test. In this they are told one member of the pair and are required to verbally give the other part of the pair. Associative abilities enale the participant to connect the stimuli and events. This test requires reasoning and transformation (Kumar et al. 2016: 4)

The closest I think I've come in this series to something semiotic.

Memory Span for Nonsense Syllables. The test measures immediate memory involving meaningless material with the help of recognition (Ebbinghaus 1985 [Memory: A Contribution to Experimental Psychology]). Recognition can help to measure subtle differences in memory abilities much better than memory recall. Although one may be unable to recall the associated details contained in the previously stated statements, one may still be able to recognize the nonsense syllables. (Kumar et al. 2016: 4)

Reminds me of my own experiences with organizing album covers or the more recent example of organizing citations for papers I'm about to read.

Efficacy of Bacopa monnieri extract on memory of intellectual sample of normal healthy medical students was evaluated after six weeks' oral administration in the dose of 150 mg twice daily. The results show a significant increase in the serum calcium levels of Bacopa group and this increase was also significant when compared with the placebo group. The raised calcium levels remained within the normal range (9-11 mg/dL). However, calcium antagonistic activity of Bacopa on the vascular and intestinal smooth muscles of rabbit and guinea pig has been reported by others (Schear & Sato 1989). (Kumar et al. 2016: 5)

Dose seems kinda low (considering the nootropic community recommends 750mg twice daily). The increase of calcium, the most significant physiological finding in this study, is disconcerting. How would it affect health? (Bones?) The final word of the paper: "We also recommend further studies to investigate role of calcium in explaining the nootropic effects of Bacopa monnieri." (p. 6)

Subramanian, Perumal; Vinoth Prasanna, Jaime Jacqueline Jayapalan, Puteri Shafinaz Abdul Rahman and Onn Haji Hashim 2014. Role of Bacopa monnieri in the temporal regulation of oxidative stress in clock mutant (cry^b) of Drosophila melanogaster. Journal of Insect Physiology 65: 37-44. DOI: 10.1016/j.jinsphys.2014.04.005

A wide assortment of behavioral, biochemical, physiological and endocrinological functions in nearly all eukaryotic organisms illustrates rhythmic variations in parallel with the day-night (light-dark) cycles. The fruit fuly (Drosophila melanogaster) offers an extremely useful system to study circadian clock function at the behavioral, molecular, cellular and organismal levels. Oxidative stress is the interference of balance between the levels of oxidants to reductants in living organisms. To scavence excess amount of reactive oxygen species (ROS), antioxidant defences including endogenous antioxidant system and exogenous antioxidant intake are essential. In this regard, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) serve as primary endagenous antioxidants to deactivate ROS in vivo, while exogenous antioxidants (vitamins C and E, polyphenols, flavonoids, etc.) assist to abolish free radicals terminating the propagation of ROS reaction. (Subramanian et al. 2014: 37)

General education portion.

Rotenone is a naturally occurring chemical with insecticidal, acaricidal and piscicidal properties and is a selective, non-specific insecticide, used for insect control (Costa et al. 2008). It exerts its toxic action by acting as a high affinity specific inhibitor of mitochondrial NADH dehydrogenase; being extremely lipophilic, it crosses cell membrane rapidly and accumulates in mitochondria elevating the generation of ROS (Miwa et al. 2003). (Subramanian et al. 2014: 38)

Kills spiders and fish. Lipophilicity is what BM is not.

In flies, blueberry extracts in diet could prolong mean lifespan, alleviate paraquat-induced mortality rate and partially reverse the decline of locomotor deficiency. The antiaging and antioxidant elevating activity of blueberry in Drosophila was at least partially associated with its interaction with genes SOD and CAT (Peng et al. 2012). (Subramanian et al. 2014: 38)

Probably why blueberries are treated as a nutraceutical or super-food these days.

The balance between the production of free radicals and antioxidant defences in organisms has important physiological and health implications. Nominal levels of ROS are continuously produced as by-products of normal oxidative metabolism, principally from mitochondrial respiration (Halliwell & Gutteridge 1999; Sohal 1997). Induced stress increases lipid peroxidation that is usually considered as an estimator of oxidative stress (Bonilla et al. 2012). Internal changes in ROS levels due to exogenous stressors could affect tissue and time-related changes in antioxidant status of Drosophila. (Subramanian et al. 2014: 41)

Another pathway: by decreasing stress, BM also decreases the threat of ROS.

Apart from the neuroprotective/neurobeneficial properties, recent evidences ascribe the temporal effect of modulating antioxidant, anxiolytic and antistress properties of B. monnieri in Drosophila and in mammals (Chowdhury et al. 2002; Jyoti & Sharma 2006; Hosamani & Muralidhara 2009). Rhythms of antioxidants have been the subject of considerable interest in recent years. Physiologically, it is known that circadian variability in antioxidants (SOD, CAT, GST, GPx and GSH) could depend on numerous factors such as meal composition, micronutrient content [|] (particularly selenium), protein dietary content, meal-related hormonal modifications and oxidative stress. (Subramanian et al. 2014: 41-43)

It was a bit disturbing to read this at 5 AM.

Krishna, R. Nivesh; R. Gayathri and Vishnu Priya 2016. Genotoxicity potential of Bacopa monnieri on oral cancer cell lines by DNA fragmentation. International Journal of Pharmaceutical Sciences Review and Research 39(1): 240-242.

Cancer is an important public health problem in most parts of the world and oral cancer is among the 10 most common cancers in the world. Squamous cell carcinoma is the most common malignant neoplasm in the oral cavity. These malignancies are often not examined until a late stage. The risk factors associated with its occurrence are tobacco and heavy alcohol consumption. Almost eighty three percent of the oral cancer patients use tobacco and the rest seventeen percent are non-users. (Krishna, Gayathri & Priya 2016: 240)

General education portion.

Bacopa monnieri is a miniature and a creeping herb usually known by the name "Brahmi". It belongs to the Scrophulariaceae family. It has been approved by several ancient Ayurvedic treatises for the enhancement of memory capacity and remedy of mental disorders. Its extract or bacosides have also shown anxiolytic effect, anti-depressant activity and anti-convulsive action. It helps to repair damaged neurons in selective places of the brain [the hippocampus] (Jyoti & Sharma 2006). This medicinal plant is analyzed phytochemically to have a chalcone. Indian Ayurvedic system suggests that this herb is useful as emetic, laxative, and as medicine in treating bad ulcers, tumors, enlargement of spleen, indigestion, inflammation and anemia. It is reported to improve the intellect and is used as medicine for the treatment of respiratory disease like asthma, hoarseness, insanity and as a potent nerve tonic, cardio tonic, and diuretic. (Krishna, Gayathri & Priya 2016: 240)

Nothing new.

The sap of the leaves is given to children for relieving bronchitis and diarrhea. Rheumatism condition can be treated by the remedy obtained from The paste of the leaves. India holds a well recorded and traditionally well practiced knowledge of herbal medicine. (Krishna, Gayathri & Priya 2016: 240)

Good to know that there are other traditional preparations besides the ghee.

The anticancer activity of the medicinal herbs selectively targets KB cells without affecting the normal cells and inhibits their growth. From the present study, it was concluded that the extract of Bacopa monnieri acts against oral cancer (KB) cells which may be due to the synergistic effect of the secondary metabolites such as flavonoids present in the extract. (Krishna, Gayathri & Priya 2016: 241)

In a dose-dependent manner.

Bin Emran, Talha Bin; Mohammad Rahman Atiar, Mir Muhammad Nasir Uddin Raju Dash, Mohammad Firoz Hossen, Mohammad Mohiuddin and Mohammad Rashadul Alam 2015. Molecular docking and inhibition studies on the interactions of Bacopa monnieri's potent phytochemicals against pathogenic Staphylococcus aureus. DARU Journal of Pharmaceutical Sciences 23: Article 26. DOI: 10.1186/s40199-015-0106-9

Effective therapeutic options to combat Staphylococcus aureus infection are still limited. And this makes a major burden to control Staphylococcus aureus. S. aureus is is a commensal Gram-positive bacterium, which colonizes in human nasal mucosa either permanently or transiently, causing severe infections eventually. But the clinical symptoms are not visualized until the immune system is affected. However, the major problem in controlling the S. aureus infection is the occurrence of multi-drug resistance produced mainly due to the misuse of antibiotics. (Emran et al. 2015: 2)

General education portion. The statistics of this pathogen are scary.

Bacopa monnieri (L.) Wellst. (Family: Plantaginaceae) is known as Herpestis monniera. It is a water hyssop or "Brahmi" and is reputed as Ayurvedic medicine. It is used for gastrointestinal discomfort, skin disorders, epilepsy, pyrexia and analgesia. Number of biologically active compounds has been isolated from this plant. GC-MS analysis of the leaf extract of this plant showed the presence of tetracyclic triterpenoids, saponin, bacosides A and B phytosterols, hersaponin, D-mannitol, flavonoids viz., luteolin-7-glucoside, apigenin-7-glucocronide, alkaloids such as nicotine and herpestine, betulic acid, β-sitosterol, stigma-sterol and its esters, aspartic acid, glutamic acid and serine. (Emran et al. 2015: 2)

Variations. Added Herpestis monniera to EBSCO search string.

Fresh leaves of B. monnieri were collected from the Chittagong University hilly forest on December 2013. [...] The extracts (yield 4.4 - 5.6% w/w) were all placed in glass Petry dishes (90 × 15 mm, Pyrex, Germany) to allow an air-dry for complete evaporation of solvent. (Emran et al. 2015: 2)

Once again picking it in the winter when its secondary metabolite content is lowest.

Results for the antibacterial activity of B. monnieri extract showed that the mean zone of inhibition (13.0-15.00 mm) produced by the extract was close to those produced by the reference antibiotics, i.e., tetracycline and ampicillin which had the zone of inhibition between 16 and 20 mm. (Emran et al. 2015: 4)

Good lord that's some powerful stuff then.

Considering the results obtained in in vitro study, it was thought worthy to perform molecular docking studies which correlate both in silico and in vitro results. Docking studies are used at different stages of drug discovery such as to predict a ligand-receptor interaction and also to rank the compounds based on the binding energies or fitness score. [...] In the docking studies of DNA gyrase binding site, luteolin among the other tested compounds has the [|] highest fitness score 53.77 compared with the highest fitness score 46.48 of ciprofloxacin. (Emran et al. 2015: 4-5)

Score for the other secondary metabolites in BM besides bacoside A.

Plant synthesizes natural products as its chemical weapon that arrests the growth of environmental microbes and some plants inhibit the growth of potential human pathogens too. In the current study, in vitro MIC of B. monnieri leaf parts, prescribed in indigenous system of medicine, that are available in the local market or growing in Bangladesh and India were evaluated against local clinical bacterial isolate of S. aureus. (Emran et al. 2015: 7)

Getting closer to the native function of these secondary metabolites.

Plant extracts having MIC below 8000 μg/ml have been reported as therapeutically effective. Our results for B. monnieri implicated a significant MIC value (below or equal to 75 μg/ml) in this study. This significance suggests that we have identified antimicrobial activity of plant that is effective for arresting the growth of S. aureus causing hospital-, -acquired- and opportunistic infections. (Emran et al. 2015: 7)

Good job.

Kongkeaw, Chuenjid; Piyameth Dilokthornsakul, Phurit Thanarangsarit, Nanteetip Limpeanchob and C. Norman Scholfield 2014. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. Journal of Ethnopharmacology 151(1): 528-535. DOI: 10.1016/j.jep.2013.11.008

Acetylcholinesterase inhibitors (AChEls) continue to be the first-line nootropics for both Alzheimer's disease and vascular dementia. Although these medications have been shown to be effective for mild to moderate dementia patients, the overall outcomes are often unsatisfactory (May et al. 2009) because of various adverse drug effects and they do not modify the disease [|] progress in the long term. Thus, when patients discontinue the medication, their symptoms return. (Kongkeaw et al. 2014: 528-529)

Is BM different in this regard? Is the modification to "cognitive function" permanent?

This plant has been used for more than 3000 years as Indian Ayurvedic medicines for improving memory, increasing brain function, or promoting longevity (Abascal & Yarnell 2011; Calabrese et al. 2008; Morgan & Stevens 2010). This medicinal plant has protective effects against β-amyloid toxicity (Limpeanchob et al. 2008) and have beneficial effects on cognitive performance (Abascal & Yarnell 2011; Calabrese et al. 2008; Morgan & Stevens 2010; Uabundit et al. 2010). (Kongkeaw et al. 2014: 529)

In other words, BM has "β-amyloid scavenging properties" (Holcomb et al. 2006; in Mitra-Ganguli et al. 2017: 3).

A recent systematic review (Neale et al. 2013) showed that Bacopa monnieri enhanced memory free recall, thus might be used as a memory enhancer. Similar efficacies were obtained from publications on Panax gingseng and modafinil in healthy, mostly young adults. (Kongkeaw et al. 2014: 529)

Not surprising. All three are nootropics.

The subject headings were Bacopa monnieri or Bacopa monniera or Herpestris monnieri or Herpestrismonniera or Monieraeuneifolia or Lysimachia monnieri or Brahmi or coastal water hyssop or watter hyssop or thyme leafed gratiola or thyme leaved gratiola or thyme leafed graticula with cognitive performance or memory. (Kongkeaw et al. 2014: 529)

My own search string just grew, too. (Herpestris has a similar duality in ending with both i and a.)

In total, nine articles remained which met our criteria (Barbhaiya et al. 2008; [|] Calabrese et al. 2008; Morgan & Stevens 2010; Peth-Nui et al. 2012; Raghav et al. 2006; Roodenrys et al. 2002; Sathyanarayanan et al. 2013; Stough et al. 2008; 2001). (Kongkeaw et al. 2014: 529-530)

My search has been pretty thorough; only one of these I didn't have on disk already.

The adverse events commonly reported in Bacopa monnieri group were gastrointestinal problems including increased stool frequency, nausea, abdominal cramps, and diarrhea. Other adverse events in [|] Bacopa monnieri group were reported such a flu-like symptoms, dry mouth, decrease in felt stress, and a reduction in number of dreams. (Kongkeaw et al. 2014: 531-532)

All familiar from personal experience, though the reduction in dreams qualified with increased lucidity, amounting to one long and continuous dream each night.

The dosage of 300 mg daily (about 50% bacosides) could be considered as a reference point for effective dosage and duration of bacopa monnieri extract for future studies and/or for treatment of cognitive impairment in clinical settings. (Kongkeaw et al. 2014: 532)

Should it?

This is supported by a study on patients with early Alzheimer's disease (n=39) given 600 mg of extract daily (300 mg twice a day) for 6 months (Goswami et al. 2011) using a clinical measurement tool 'Mini Mental State Examination (MMSE)'. It showed cognitive improvement in terms of time, places and persons as well as a better quality of life (reduced irritability and insomnia). (Kongkeaw et al. 2014: 532)

The reduction in irritability is probably why some call it the herb-of-grace despite it commonly designating a wholly different plant.

The compounds extracted from Bacopa monnieri which are believed to increase cognitive performance and exhibit neuroprotective properties include steroidal saponins (bacoside A, i.e., bacosides A₂ and A₃; bacoside B, i.e., bacopaside N₁, N₂, IV and V, bacopasides I-VIII; bacopaside X; and bacopasaponins A-G) and triterpenoidal saponins (jujubogenin and pseudojujubogenin) (Calabrese et al. 2008; Limpeanchob et al. 2008; Morgan & Stevens 2010; Rajani 2008; Russo & Borrelli 2005) although extract contain many other potentially active compounds (Aguiar & Borowski 2013). Comparisons have been helped by the use of standardized Bacopa monnieri-based nutraceutical extracts usually expressed as bacoside A content. Nevertheless, without being sure about the active ingredients, this is not a guarantee of consistency. Also, there is little data in the public domain on bioavailability, metabolism, and pharmacokinetics of these compounds in vivo. (Kongkeaw et al. 2014: 533)

I wonder if reading every paper I've downloaded could amount to even a brief on the functions of different phytoconstituents.

Such a complex spectrum of actions, in mostly animal studies, might reflect varying activity profiles of individual components contained in the Bacopa monnieri extracts. Likewise, increased attention and alertness may be a distinct pharmacological target from an action in dementia patients having dysfunctional cerebral blood flow or degenerating neuronal function. Thus, multiple targets may explain inconsistencies between studies and the variations between different extracts probably also account for inter-study discrepancies. (Kongkeaw et al. 2014: 534)

Multi-pharmaceutical utilization.

Karataş, Mehmet and Muhammad Aasim 2014. Efficient In Vitro Regeneration of Medicinal Aquatic Plant Water Hyssop (Bacopa monnieri L. Pennell). Pakistan Journal of Agricultural Sciences 51(3): 667-672.

Medicinal plants are being used since ancient times for curing of disease and are still in use as traditional medicine or as a source of medicinally important compounds. Water hyssop (Bacopa monnieri L. Pennel) has great importance in traditional medicine system due to active compounds like alkaloids, saponins, flavonoids, betulic acid, stigmasterol, beta-sitosterol and bacopasaponins (Ali et al. 1999; Chatterji et al 1963; 1965). It is also used as a cardiac tonic, brain tonic to enhance memory development, and to provide relief to patients with anxiety or epileptic disorders in traditional medicinal systems of Pakistan and India (Chopra 1958; Mukerjee & Dey 1996; Vijaykumar et al. 2010). It possesses anti-inflammatory, analgesic, antipyretic and diuretic activity (Vohora et al. 1997; Stough et al. 2001). It is also used to treat insanity, epilepsy, hoarseness, enlargement of spleen, snake bite, rheumatism, leprosy, eczema, ring worm (Basu & Walia 1994) and treat anxiety, epilepsy, bronchitis, asthma, irritable bowel syndrome and gastric ulcers (Shakoor et al. 1994). (Karataş & Aasim 2014: 667)

Nothing but variations.

The plant is perennial creeping herb with relatively thick succulent leaves that are oblanceolate that are arranged oppositely on the stems. It commonly grows in damp and marshy places throughout South Asia up to an altitude of 1320 m. The plant bears small, white coloured flowers with four or five petals. (Karataş & Aasim 2014: 667)

So, leaves not oblong and flowers not purple, as reported elsewhere.

Largia, Muthiah Joe Virgin; Govindan Pothiraj, Jayabalan Shilpha and Manikandan Ramesh 2015a. Methyl jasmonate and salicylic acid synergism enhances bacoside A content in shoot cultures of Bacopa monnieri (L.). Plant Cell Tissue and Organ Culture 122(1): 9-20. DOI: 10.1007/s11240-015-0745-z

Bacopa monnieri (L.), commonly known as 'Brahmi' or 'memory herb' is a highly valued medicinal plant extensively used in the Ayurvedic system of Indian medicine for more than 3000 years (Nisha et al. 2003). It has been delineated to possess anti-inflammatory, anti-cancer, anti-oxidative, antipyretic and analgesic properties (Elangovan et al. 1995; Mathur et al. 2010). The plant is very popularly used to enhance memory and to treat neuro pharmacological disorders and anxiety (Rastogi et al. 1994). (Largia et al. 2015a: 9)

Memory herb containing memory molecules. Memory, memory, memory.

In vitro shoot cultures can provide an alternative source to natural plant population for the large scale production of remarkable secondary metabolites. Praveen et al. (2009) studied the effects of semisolid and liquid media with plant growth regulators on bacoside A accumulation and found the highest quantity (11.9 mg/g dry weight) of the saponin accumulation in liquid medium. In 2010, Naik et al. (2010) formulated a suitable media composition for bacoside A accumulation in in vitro shoot cultures. They have specified that media supplemented with 2% sucrose and pH set at 4.5 would be suitable for producing about 13.09 mg/g dry weight of bacoside A. Even though some attempts have been made to improve the production of bacosides, the quantity produced was not satisfactorily high to meet the industrial needs [of] the compound. Hence we planned to carry out elicitation strategies to further increase the amount of the triterpenoid saponin under in witro conditions. (Largia et al. 2015a: 10)

Those are indeed quantities higher than what is reported elsewhere even from elite genotypes.

Elicitation is a process of stimulating the production of secondary metabolites by the use of elicitor molecules (Brooks & Watson 1986). Elicitors are external stimuli capable of prompting changes in the plant cell leading to a series of reactions, drastically favouring the accumulation of secondary metabolites. They bind to a receptor protein in the plasma membrane, which eventually activate particular genes as a part of defense response through signal transduction pathways, resulting in the synthesis of secondary metabolites (Sudha & Ravishankar 2002). Eliciting the cultures with chemical substances has been the most reliable method and a useful biotechnological tool for secondary metabolites production in elevated amounts (Radman et al. 2003; Vasconsuelo & Boland 2007). (Largia et al. 2015a: 10)

Here the native function of these secondary metabolites appear to be laid bare: defence. In this regard the bacosides are not different from capsaicin and caffeine.

Among the various elicitors, methyl jasmonate (MJ) and salicylic acid (SA) have been very well documented for the increased production of triterpenoid saponins in plant cell cultures (Lambert et al. 2011). MJ, a volatile methyl ester of the plant hormone jasmonic acid has been identified as a signaling molecule in biotic and abiotic stresses (Creelman & Mullet 1995). According to Yu et al. (2002), MJ aids in the formation of defense compounds by implicating in signal transduction pathway that induces particular enzymes to produce those molecules. Another stress signaling molecule, SA is extensively studied for its role in influencing plant resistance to pathogens (Rao et al. 2000). In the last decade, SA emerged as a key-signaling compound that is involved in the activation of certain plant defense responses (Kang et al. 2004). (Largia et al. 2015a: 10)

So much for the general idea that "These secondary metabolites are not directly related to the physiological growth of plants but help in the plant's longevity." (Leonard et al. 2017: 2) - Defense is much more specific.

In particular both the elicitors were found to enhance triterpenoid saponins such as asiaticoside (7.12 mg/g DW) in Centella asiatica hairy root cultures upon elicitation with 0.1 mM MJ for 3 weeks (Kim et al. 2007) and glycyrrhizin in Glycyrrhiza glabra by the addition of MJ and SA (Shabani et al. 2009). [↩] Recently, Sharma et al. (2013) observed 1.5-fold enhancement of triterpenoid saponin in B. monnieri by the addition of 50 μM MJ. However, to meet the growing demand futher increase in bacoside quantity is very much needed. (Largia et al. 2015a: 10)

How related are BM and Centerlla asiatica?

Cells at different stage of growth have different levels of mRNA and proteins and may yield varied responses in terms of cell growth and secondary metabolite production (Chong et al. 2005). Optimization of culture age is one of the critical factors to improve the bacosides production in shoot culture of B. monnieri. Therefore we decided to standardize the optimal harvest time for highest biomass accumulation and bacoside A production. Optimal harvest time was evaluated in terms of biomass accumulation and bacoside A production. Plant biomass reached a maximum level of 1.83 g DW on 3cd week of culture and further increase or decrease in harvest time has led to reduction of biomass accumulation. [...] On increasing the culture period, bacoside A production declined in the shoot cultures of B. monnieri. Hence at 3 weeks culture duration the maximum biomass accumulation and bacoside A production were achieved. (Largia et al. 2015a: 12)

More interesting, and quite necessary, tidbits for growers and harvesters.

Amongst the four different concentrations, the treatment with a combination of 25 μM MJ and 25 μM SA for about 3 weeks caused a spectacular improvement in bacoside A production. Bacoside A₃ was enhanced because of this combined elicitation strategy up to 3.5-fold in comparison to the control. (Largia et al. 2015a: 16)

The results are certainly spectucular.

Singh, Rajbir; Ramakrishna Rachumallu, Manisha Bhateria, Jagadeesh Panduri and Rabi Sankar Bhatta 2015. In vitro effects of standardized extract of Bacopa monniera and its five individual active constituents on human P-glycoprotein activity. Xenobiotica 45(8): 741-749. DOI: 10.3109/00498254.2015.1017752

Herbal drugs are becoming popular in spite of the fact that their mechanism of action being generally unknown, lack of evidence of efficacy and inadequate herb-drug interactions. It has been estimated that about one-third of the adults in the developed nations and more than 80% of the population in developing countries use herbal medicines with the perception that herbal drugs are safe and devoid of any side effects. (Singh et al. 2015: 741)

Yup. Seems to work, seems to not be toxic, good enough, right? We'll learn.

Most often, these herbal drugs are co-administered with drugs without prescription, which increases the chances of potential derb-drug interaction which may have clinical significance (Colalto 2010; Izzo & Ernst 2001). Alteration in the expression or activity of drug metabolizing enzymes and membrane transporters has been identified as a major underlying mechanism of such herb-drug interactions (Evans 2000; Walter-Sack & Klotz 1996). (Singh et al. 2015: 741)

Where is the data for how BM is consumed by regular users?

P-glycoprotein (P-gp) is an ATP-driven efflux pump that is found in all organs, especially in brain, intestine and other drug eliminating organs. This membrane protein plays an important role in influencing the oral bioavailability of several clinically important drugs (Watkins 1997). Additionally, intestinal enterocytes express high amount of P-gp efflux transporters, and form the first line of barrier for orally administered drugs. P-gp transporter that is present on enterocytes effluxes the P-gp substrates from blood into the intestinal lumen and therefore any alteration in its activity would eventually result in altered plasma level of P-gp substrate drugs (Funakoshi et al. 2003; Moriguchi et al. 2007; Trauner et al. 1997). (Singh et al. 2015: 741)

I know some of those words.

In today's fast-paced life, it has been observed that cerebral abilities are waning with advancing age and factors such as emotional stress. To alleviate the mental deterioration affecting numerous people around the world, several plants have been used in traditional system of medicine that could act as nootropic agent. One plant that has been used as brain tonic and restorative in debilitating conditions is Bacopa monniera (BM), commonly known as Brahmi. BM is the second most touted herb in Ayurveda and widely used for the memory enhancement in children and adults from time immemorial (Russo & Borrelli 2005). BM also possess many other pharmacological activities like antidepressant (Sairam et al. 2002), neuroprotectant (Uabundit et al. 2010), anticonvulsant (Shanmugasundaram et al. 1991), antioxidant (Bhattacharya et al 2000; Tripathi et al. 1996), bronchodilator (Dar & Channa 1997), antiulcerogenic (Rao et al. 2000) and anticancer properties (Elangovan et al. 1995). (Singh et al. 2015: 742)

How many of these lists do I need? How many variatinos for "memory enhancer" are there?

Bacosides Enriched Standardized Extract of Bacopa (BESEB) has been developed and patented by CSIR-CDRI, Lucknow, India (http://www.cdriindia.org/Memory_Sure.pdf). Herbal products of BM containing BESEB are marketed not only in India but also across worldwide. The extract of BM has been standardized to 55±5% bacoside A and B. Contrary to the earlier studies, it has been now widely reported that bacoside A and B are not single chemical entities but are mixture of various triterpenoid saponins (Kawai & Shibata 1978). (Singh et al. 2015: 742)

Nice. I needed a shorthand for that.

Oral route of drug deliveri is the preferred route for drug administration. P-pg plays a crucial role in limiting the oral bioavailability along with physical processes and CYP-mediated drug metabolism. Furthermore, the P-gp is vulnerable to modulation by interacting with various xenobiotics. In recent studies, it has been demonstrated that BM extract and its individual constituents inhibited the CYP3A activity. Since CYP3A and P-gp shares substrate, inhibitor and inducer specificity, it is important to evaluate the effect of BM extract and its constituents of P-gp activity. It has been reported that compounds inhibiting the CYP3A4 activity also inhibit the P-gp-mediated efflux (Wacher et al. 1995) and influence the bioavailability of drugs. (Singh et al. 2015: 746)

Useful. Though, is there a way to check if certain drugs are metabolized via P-gp or cytochrome P450 enzymes?

It has been well reported that some compounds stimulate the ATPase activity while others inhibit its activity and this property will depend on their affinity towards catalytic and inhibitory site of protein (Dey et al. 1997; Zhu et al. 2006). In the present study, we observed inhibition of both basal activity as well as verampamil-stimulated ATPase activity in P-gp ATPase assay, which suggests that BM extract and its five individual active constituents have affinity towards P-gp. (Singh et al. 2015: 747)

I know some of those words. Need to learn more about the ATPs.

Maximum inhibition of P-gp was observed with positive control verapamil followed by bacoside II, bacoside A3, bacopasaponin C, bacopaside I, bacoside A and least inhibition with BM extract. Moreover, BM extract did not decrease the basal to apical transport of Rh123, but the significant decrease in efflux ratio of Rh123 suggests the modulation in P-gp activity. Although decreased transport of Rh123 with Bm did not follow the typical P-gp mediated inhibition pattern, the decreased efflux ratio (P_{app BA/AB}) suggested that interaction has occurred that would eventually alter the P-gp substrate drug pharmacokinetics. (Singh et al. 2015: 748)

Another instance of various phytoconstituents of BM having variable effects.

However, additional work is warranted to extrapolate these in vitro findings to in vivo situations. Therefore, until proven safe, care should be taken regarding the co-administration of P-gp substrate drugs along with BM. (Singh et al. 2015: 748)

Will do.

Shahid, Muhammad; Fazal Subhan, Ihsan Ullah, Gowhar Ali, Javaid Alam and Rehmat Shah 2016. Beneficial effects of Bacopa monnieri extract on opioid induced toxicity. Heliyon 2(2): e00068. DOI: 10.1016/j.heliyon.2016.e00068

Herbal medicine has shown promise in relieving abstinence symptoms and anxiety during heroin detoxification (Liu et al. 2009). Bacopa monnieri (Linn.) Pennell, a reputed nootropic plant (Russo & Borrelli 2005) from family Scrophulariaceae, has been studied widely for its cognitive enhancing (Vollala et al. 2010), antidepressant (Sairam et al. 2002), antihypertensive (Kamkaew et al. 2011), anti-asthmatic (Dar & Channa 1997), antiulcer (Sairam et al. 2001), analgesic (Abbas et al. 2011), neuroprotective (Limpeanchob et al. 2008), hepatoprotective (Sumathy et al. 2001) and nephroprotective properties (Sumathi & Devaraj 2009). (Shahid et al. 2016: 3)

"There were no improvements in impulsivity at any stage of this study." (Kean, Downey & Stough 2016: 58)

The use of Bacopa monnieri as adjuvant therapy in the management of opioid tolerance may be beneficial (Rauf et al. 2011a). (Shahid et al. 2016: 3)

Adjuvant therapy, "also known as adjunct therapy, add-on therapy, and adjuvant care, is therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments." - The only issue being perhaps the enzymatic interactions (see pharmacokinetic studies), and that BM is probably best used as as a prophylactic.

In this study, pretreatment with standardized mBME restored opioid induced elevation of serum ALT, AST and creatinine and provided protection against histopathological changes in the liver and kidneys after 14 and 21 days. The hepato- and nephro-protective effect of mBME at the same dose (40 mg/kg) has been reported by Sumathi and Devaraj (2009) against morphine. (Shahid et al. 2016: 18)

More positive effects, though the mechanism once again boils down to antioxidation.

Bacopa monnieri by virtue of antioxidant effect of its major component, bacoside-A inhibits morphine induced brain oxidative stress by improving the activity of ATPase and maintaining the sodium, potassium, calcium and magnesium ionic equilibrium (Sumathi et al. 2011) as well as normalizing the activities of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADPH dehydrogenase and cytochrome c oxidase (Sumathy et al. 2001). Therefore, blocking of oxidative stress by natural antioxidants such as Bacopa monnieri may be useful in the development of new therapy for opiate abusers. However, the protective effect of Bacopa monnieri mediated by its antioxidant property against morphine or stress heroin induced hepatotoxicity and nephrotoxicity needs further investigation for direct evidence linking reactive oxygen syecies with oxidative/redox stress injury by assay of antioxidant enzymes, malondialdehyde or protein markers. (Shahid et al. 2016: 20)

The great normalizer, again. Further research suggestion is on point.

Hussain, K; A. K. Abdussalam, Chandra P. Ratheesh and Salim Nabeesa 2011. Heavy metal accumulation potential and medicinal property of Bacopa monnieri: A paradox. Journal of Stress Physiology & Biochemistry 7(4): 39-50.

Bacopa monnieri (L.) Pennell is a fast growing wetland species and is well adapted to thrive in polluted areas which receive regular flushing of sewage waste and industrial effluents. Lenka et al. (1992) reported that B. monnieri accumulate mercury in the roots and shoots of plants growing in the wetlands in the vicinity of Choralkali industry. (Hussain et al. 2011: 40)

Another one of these papers advising BM as a phytoremediator.

During growth for 12 days, accumulation of mercury was maximum in roots followed by stem and leaves during all intervals. Mercury accumulated in the root tissue remained unchanged during growth compared to the stem and leaf tissue which showed enhanced rate of accumulation. (Hussain et al. 2011: 43)

Perhaps the whole plant should not be used when wild plants are collected?

Collection of B. monnieri plants from contaminated wetlands is a common practice of manufacturers of Ayurvedic medicines and food supplements and consumption of these products by human beings will lead to serious health hazards. (Hussain et al. 2011: 47)

Not good at all.

The medicinal property and wide use of Bacopa monnieri as an ingredient of many Ayurvedic medicines and food supplements on one hand and the bioaccumulation potential and phytoremediation efficacy on the other are paradoxical. (Hussain et al. 2011: 47)

What is paradoxical is that it's a metal chelating agent that removes excess of toxic metals from the bloodstream.

Pandey, Surya P.; Hermant K. Prasad and S. Prasad 2015. Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice. PLOS ONE 10(7): e0131862. DOI: 10.1371/journal.pone.0131862

Development of eLTP [early long term potentiation] in the hippocampus, the gateway of learning, memory and cognition, requires sequential activation of the two major ionotropic glutamate receptors called α-amino-3-hydroxy-5-methyl-4-isokazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors at glutamatergic synapse. Following the presynaptic neuronal signaling, glutamate is released in the synaptic cleft and activates the AMPA receptors at the post synaptic density. Glutamate activated AMPA receptors cause depolarization of the postsynaptic neuronal membrane, which in turn, acts as a signal for opening of the NMDA receptors by removal of its Mg²⁺ block to achieve post synaptic potential (PSP) and allows diffusion of extracellular Ca²⁺ and Na⁺ into postsynaptic neurons. This leads to rise in the intracellular Ca²⁺ level, binding of Ca²⁺ with calmodulin (CaM) and activation of CaMKIIα, which in turn achieve Ca²⁺-dependent synaptic synaptic plasticity mediated alterations in the density and activity of both the glutamate receptor typees on the post synaptic density. AMPA receptors possess heterotetrameric structure consisting of four subunits designated either as GluA1-GluA4 or GluR1-GluR4 or GluRA-GluRD). Among them, the GluR2 subunit plays important role in synaptic plasticity as it is inserted into membrane during generation of LTP or it is internalized into cytosol during LTD. (Pandey et al. 2015: 2)

A more thorough account of the the calcium dependent protein kinase described by McPhee et al. (2016: 73).

Bacopa monnieri, commonly known as Brahmi, is one of the most common Indian herbs that are known for its nootropic role in array of neurological disorders and memory impairments. Its alcoholic extract has been shown to possess antioxidant activity based on number of studies on various animal disease models and used in neuroprotection, cognition, depression, anxiety, epilepsy, cancer and inflammation related disorders. Existing literature suggests that Bacopa extract possesses neuroprotective effects on various memory related areas of the brain i.e. frontal cortex, hippocampus and striatum, and enhance learning and memory due to its antioxidant properties. (Pandey et al. 2015: 2)

Slightly different than previous brief reports that mention only the hippocampus. Otherwise a standard list of positive effects.

STZ-induced DM2 leads to increase in blood glucose content, water intake and urine output and CDRI-08 reverses them towards their normal values. [...] Our data clearly indicates that streptozotocin treatment significantly increases the blood glucose levels compared to that in the control mice (P<0.05) i.e. it successfully produces a diabetic mice model, which can be used for further experiments. Our data suggests that lower dose of CDRI-08 (50- or 100 mg/kg BM) does not affect the blood glucose content whereas its higher doses (150-, 200-, 250- and 300 mg/kg BM) lead to significant decline in the blood glucose content in general and above 200 mg/kg BM in particular also have pronounced antidiabetic effects (P<0.05). (Pandey et al. 2015: 8)

At this point these kinds of results are expected. (The various ameliorative effects of BM should be well-known.)

Data on the effects of CDRI-08 alone reveals that it does not affect the pancreatic secretion of insulin and its level in the blood. (Pandey et al. 2015: 9)

Good to know. It wouldn't be a "normalizer" if it threw something like insulin out of whack.

The data clearly suggests that the CDRI-08 alone also has memory enhanging effects but extent of effects of its corresponding doses is more pronounced when they are administered to STZ-treated DM2 mice. (Pandey et al. 2015: 11)

The summary might read: BM enhances memory but especially when there is a memory disorder to ameliorate, first.

It was observed that STZ mice exhibited significant decline in body weight compared to the normal control mice, and the treatment of STZ mice with CDRI-08 doses up to 200 mg/kg BM had no remarkable effects on the body weight, however, the dose above it i.e. 250 or 300 mg/kg BM caused slight increase in the body weight in CDRI-08 control as well as DM2 mice but the extent of the body weight increase was lower in DM2 mice. (Pandey et al. 2015: 15)

This is also corroborated later: "mice administered with BM showed slight increase in body weight as compared with the control group at week 4" (Hosamani, Krishna & Muralidhara 2016: 438).

In this regard, our results suggest that CDRI-08 which, in its lower dose range, has no effects on the serum level of insulin, also has no effects on insulin resistance values, however, the its higher doses decrease the insulin resistance as evident from our HOMA-IR dat, which can be correlated with its anti hyperglycaemic effects. (Pandey et al. 2015: 15)

This could have profound consequences for human subjects consuming high quantities of BM.

Recovery of the memory loss by higher doses of CDRI-08 can be correlated with decline in insulin resistance which could lead to decline in the serum glucose towards normal control value as evident from our data whereas pro cognitive effects on its lower doses might be associated with decline in oxidative stress as observed by us. (Pandey et al. 2015: 16)

Online sources say exercise decreases insulin resistance, so might be a good thing. Will hang on to this tidbit, since even "neutral" effects could be significant in the long run. Likewise with the increased calcium content in blood. Ultimately, these should be considered in conjunction with BM's more direct effects on digestion.

Further, due to high blood glucose and oxidative stress, blood brain barrier has been reported to become more leaky to harmful substances which, in turn, may exaggerate the effects of oxidative stress in the brain and alter its structure and function due possibly to apoptosis of neurons. This may altogether severely compromise the function of various memory related regions in the brain including hippocampus. (Pandey et al. 2015: 16)

Another interesting mechanism where some damage may lead to further damage in a "witch's circle" type ordeal.

The anti diabetic potential of the higher dose of CDRI-08 (i.e. 150-300 mg/kg BM) by increasing the insuling sensitivity is a novel observation in our study, which is consistent with data reported earlier on the anti diabetic role of Bacopa monnieri whole extract (Yoshikawa et al. 2001). (Pandey et al. 2015: 17)

The cited source may be erroneous, perhaps they meant Borelli et al. (2003)? Nevertheless, Yoshikawa et al. treat the triterpene oligoglycosides and the "gastric emptying" in rats, which may be enlightening on its own right.

We have characterized basis of memory enhancing function of CDRI-08 which is only a fraction of the whole extract of Bacopa monnieri rich in bacosides A and B 9 (57.5%). Therefore, it is likely that when the active principles i.e. bacosides A and B are separated from other ingredients of the whole extract and which might have been active at low dose being together, may lose its efficacy and thus may require high dose to produce the similar effects as brought by the Bacopa monnieri total extract. This could be one of the possible reasons for a need of higher dose range of CDRI-08 in correcting the memory impairments along with its antidiabetic effects by increasing the targeting function of the insulin in glucose metabolism. (Pandey et al. 2015: 17)

The whole plant extract may even be more effective that BESEBs since the whole plant contains some 60+ ingredients, some of which have already proven efficacy. It might be the case that bacoside A was called out as the primary bioactive phytoconstituent of BM too early, before all the necessary data to make such a judgement, was (and probably still isn't) in.

Łojewski, Maciej; Bożena Muszyńska, Agata Smalec, Witold Reczyński, Włodzimierz Opoka, Katarzyna Sułkowska-Ziaja 2014. Development of Optimal Medium Content for Bioelements Accumulation in Bacopa monnieri (L.) In Vitro Culture. Applied Biochemistry and Biotechnology 174(4): 1535-1547. DOI: 10.1007/s12010-014-1095-8

Bacopa monnieri (L.) Pennell (water hyssop), known locally in India as Brahmi or Jalanimba, is one of the most important plants in the traditional Hindu system of [|] medicine, Ayurveda. Brahmi name comes from the word Brahma, one of the main gods of Hinduism. B. monnieri is used in India for 5,000 years to treat epilepsy and insomnia, as a sedative and abolishing raw anxiety. Indian materia medica (Bhavprakash Nighantu 1,500 years AD) recommends this resource as a means of improving memory and concentration. (Łojewski et al. 2014: 1535-1536)

The connection with the god is mentioned on Wikipedia. Probably the source for this bit, as nothing is added besides the fact.

Extracts from B. monnier are used for blood purification from heavy metals, due to their ability to accumulate organic compounds contained therein (Ahire et al. 2013). This raises the possibility of obtaining raw material enriched in beneficial to human body compounds (anthranilic acid-L₁ vitamin; L-tryptophan; serine) and micronutrients (Mg and Zn) for targeted physiological effects. (Łojewski et al. 2014: 1536)

Finally a source for this claim.

The fresh material might be even more effective in treatment of diseases. Due to limited information on the content of macroelement and microelement (playing important role in human metabolism by building blocks and being enzymes activators) in the fresh material of B. monnieri, it is necessary to determine bioelements quantitatively and to assess their ability to accumulate in this material under fully controlled conditions of in vtiro culture. (Łojewski et al. 2014: 1536)

Interesting suggestion. Some redditor wrote that he had the plant in an aquarium and ate a fresh leaf every day.

The aim of present research was to evaluate the influence of the necessary amino acids for the human body (anthranilic acid, L-tryptophan, serine) on accumulation of the selected bioelements. Anthranilic aid (L₁ vitamin) and serine are precursors of L-tryptophan, which in turn is a direct precursor of serotonin. L-tryptophan when ingested, on the contrary to serotonin, easily crosses the blood-brain barrier in the central nervous system, where it is efficiently converted to serotonin. In the central nervous system, serotonin takes part in neuron to neuron communication and appears to enhance the perception of well-being and modulate the intensity of emotional states. (Łojewski et al. 2014: 1536)

Good to know. Falls under "general education".

Metal can exist in the environment as an element or as a compound with other inorganic or organic elements (chelates). (Łojewski et al. 2014: 1357)

So that's what that means.

De, Kakali; Susmita Chandra and Mridula Misra 2009. Assessment of the effect of Bacopa monnieri (L.) Wettst. extract on the labeling of blood elements with technetium-99m and on the morphology of red blood cells. Revista Brasileira de Farmacognosia. Sep 2009 19(3):664-671. DOI: 10.1590/s0102-695x2009000500003

Extensive investigations (Russo et al. 2005; Kishore & Singh 2005; Bhattacharya et al. 2000) indicate that the extract of BM facilitated learning acquisition, improved retention of learning (memory) and to increase the activity of antioxidative enzymes (e.g. superoxide dismutase (SOD), glutathione peroxidase and catalase) (Jyoty et al. 2007). (De, Chandra & Misra: 665)

Variations for memory enhancement.

In Nuclear medicine technetium-99m (99mTc) has been the most utilized radionuclide both in diagnosis nuclear medicine procedures and in basic scientific research [...]. This wide use in nuclear medicine is due to its optimal physical characteristics, convenient availability from Mo-99/Tc-99m generator and negligible environmental impact [...] [↩] There are several important applications of 99mTc labeled red blood cells (99mTc-RBC), the most important being cardiovascular nuclear medicine. Some other applications include the blood pool of other organs, detection of gastrointestinal bleeding sites, and determination of RBC mass in patients. (De, Chandra & Misra: 665)

General education. This is probably more precise than using garlic and smelling the wounds.

Sequential steps of the intracelluralrly labeling process of blood constituents include: (1) transmembrane transport of reductase agent (Sn²⁺) and 99mTcO4 ions into the internal compartment of the RBC, (2) reduction of 99mTc(99mTcO4) by Sn²⁺, and (3) subsequent binding of the reduced 99mTc to hemoglobin (Dewanjee et al. 1982; Abreu et al. 2006). The band-3 anion transport system and calcium channels may be involved in transport of these ions (Callahan & Rabito 1990; Sampson 1996). (De, Chandra & Misra: 665)

Note that BM "significant increase in the serum calcium levels" and has "calcium antagonistic activity" (Kumar et al. 2016: 5).

There are evidences that various medicinal plants can affect either radiolabeling or biodistribution of red cells in the context of the nuclear medicine clinic, and a number of workers have turned their attention to in vitro testing of the drug (synthetic/natural) with 99mTC labeled blood cells [...] We have studied the BM extract effect on the labeling of RBC with 99mTc and the fixation of this radionuclide to insoluble fraction of plasma (plasma proteins) and blood cells (blood cells proteins). The results of this study showed that BM extracts reduced the fixation of radioactivity in plasma proteins and blood proteins. (De, Chandra & Misra: 668)

I am not surprised. Should "anti-radioactive" be included in the list of positive effects?

The labeling of blood constituents could decrease due to the action of drugs (natural and synthetic) in (1) binding at the same sites on the blood constituents, (2) direct inhibition (chelation action) of the stannous (Sn⁺²) and pertechnetate ions (99mTcO^-), (3) direct oxidation or generation of free radicals that could oxidize the stannous ion, (4) antioxidant action impeding or decreasing the stannous ion oxidation, and (5) alteration of the plasma membrane structure or modifying the transport systems of stannous and pertechnetate ions into cells. (De, Chandra & Misra: 669)

With BM these two (metal chelation and anti-oxidant activity) sound like prime suspects.

Experiments with different extracts of medicinal plants are in progress to evaluate the possibility of the generation of these free radicals. Furthermore, this study suggests that the aqueous extracts of Bacopa monnieri could present antioxidant action and/or effects on the membrane structures involved in ions transport altering the radiolabeling of blood constituents with 99mTc and that precaution should be taken in examinations of nuclear medicine based on this procedure in patients using Bacopa monnieri extracts. (De, Chandra & Misra: 669)

Noted. Falls into the category of interesting endogenous interactions.

Ribeiro, Jose Pedro N.; Fernanda C. S. Tiberio and Alexandre A. de Oliveira 2015. The effect of competition on Bacopa monnieri zonation in an temporarily open/closed tropical estuary. Estuarine, Coastal & Shelf Science 163: 231-234. DOI: 10.1016/j.ecss.2015.06.029

Plant competition is one of the most important factors determining plant zonation, and competitive interactions play a major role in ecosystem structure and function (Peyre et al. 2001; Zhang 2010). As different species vary in their responses to abiotic drivers, the environment modulates biotic interactions. Therefore, plant competition is influenced by local abiotic conditions, and the outcome species (and consequently, the plant assemblages) can vary extensively along an abiotic gradient (Costa et al. 2003; Emery et al. 2001; Ribeiro et al. 2011a). (Ribeiro, Tiberio & Oliveira 2015: 231)

Must be the first straight up ecological paper in this series. Hopefully will prove enlightening as to the most suitable environment for non-micropropagated BM.

Bacopa monnieri L. Pennel (PLantaginaceae) is a small herb widely distributed in the tropics and subtropics, living within or adjacent to water bodies. It is also commonly used for freshwater aquariums, in which it can live permanently submerged. [...] where we performed the present work, B. monnieri forms large monospecific stands near the bar but is absent upstream. Vertically, it occupies deeper (but not the deepest) zones. As this species can live either completely or partially submerged in freshwater or live unsubmerged, we hypothesized that its absence from the shallower, deeper and freshwater zones is due to competitive displacement. To test this hypothesis, we transplanted this species to these areas and artificially removed competition. (Ribeiro, Tiberio & Oliveira 2015: 231)

Valuable details, much more specific than the regular "found in wet, damp and marshy areas".

The selected model included salinity, which was positively related to covering area. It also included competition and the interaction of flooding and salinity, which were both negatively related with turf covering area. Bacopa monnieri has low nutritional requirements (Fang et al. 2007), and soil under the canopy is much richer than the poor sandy soil B. monnieri is able to live. Therefore, melow-ground competition was unlikely to be an important factor. In contrast, shading is an important limiting factor of submerged macrophytes (Philips et al. 1978). Although an experiment specifically designed to separate below- and above-ground competition would be informative, it is likely that the competitive displacement experienced by B. monnieri in Forest was due to light limitation. The performance of turfs in Forest Pots in the first month of the experiment was equivalent to that of Control. Furthermore, plants in the pots flowered. Plants in Forest Pots and Control experienced very different flooding cycles; however, B. monnieri can survive in both conditions. The selected model did not include flooding but related competition with a large reduction in turf covering area. (Ribeiro, Tiberio & Oliveira 2015: 232)

More valuable details about the plant that are absent from even the more informative micropropagation studies.

Although competition is the key influence on [|] B. monnieri occurrence, it is likely that it would perform better when less flooded in the absence of competitors. Thus, frequent flooding is an ecological refuce rather than a physiological demand. (Ribeiro, Tiberio & Oliveira 2015: 232-233)

Thus, BM might live in damy and marshy areas because it amounts to less competition from other plants.

We never observed herbivory on B. monnieri in its natural zone of occurrence. However, the plants in the pots were severely injured by ant herbivory. Ant herbivory was also observed in another experiment conducted at the study site, in which Crinum americanum L. were preyed upon when transplanted out of the water. Both B. monnieri and C. americanum are soft-tissue plants with no physical defence mechanisms but with strong allelopathic properties (Takao et al. 2011), suggesting they rely on chemical defences to avoid herbivory. This interpretation is consistent with the findings of Morrison and Hay (2011) that indicate high investment in chemical defences among tropical macrophytes. (Ribeiro, Tiberio & Oliveira 2015: 233)

Hence the curious multifunctional secondary metabolites.

Wangdi, Kencho and Indira P. Sarethy 2016. Evaluation of Micropropagation System of Bacopa monnieri L. in Liquid Culture and Its Effect on Antioxidant Properties. Journal of Herbs, Spices & Medicinal Plants 22(1): 69-80. DOI: 10.1080/10496475.2015.1020404

Bacopa monnieri (Scrophulariaceae), commonly known as water hyssop or Brahmi, is an important medicinal plant found in the Indian subcontinent, widely available in several formulations for its memory enhancing and [|] antioxidant properties; it is also useful in the treatment of cardiac diseases, insomnia, depression and epilepsy. (Wangdi & Sarethy 2016: 69-70)

Also Austria, and Meso- and South-America.

There is an increasing demand for B. monnieri plant material, resulting in overharvesting. Additionally, poor seed setting, low seed viability, and frequent seedling mortality in early stages makes natural rejuvenation in the wild a slow process. (Wangdi & Sarethy 2016: 70)

From what little I've met about the wild conditions, it is a rather picky and difficult plant.

Priyanka, Hannah P.; Ran Vijay Singh, Miti Mishra and Srinivasan ThyagaRajan 2013. Diverse age-related effects of Bacopa monnieri and donepezil in vitro on cytokine production, antioxidant enzyme activities, and intracellular targets in splenocytes of F344 male rats. International Immunopharmacology 15(2): 260-274. DOI: 10.1016/j.intimp.2012.11.018

Bidirectional communication between the neuroendocrine system and immune system through hormones, neurotransmitters, and cytokines maintains homeostasis and health status of an individual. In the periphery, immune responses are regulated through the sympathetic noradrenergic (NA) nerve fibers in the lymphoid organs (bone marrow, thymus, spleen, and lymph nodes) which release norepinephrine (NE) and modulate immune responses by binding to adrenergic receptors on the immune cells. With advencing age, there is an age-associated decline in sympathetic NA innervation in the spleen and lymph nodes along with significant loss of T cell responses including proliferation and cytokine production. Accumulation of free radicals due to loss of antioxidant enzyme activities is one of the major reason for this sympathetic neurodegeneration in the spleen and lymph nodes. (Priyanka et al. 2013: 260)

Something endosemiotic. Could the communication paradigm apply elsewhere?

Brahmi is a natural herb widely used in Ayurvedic medicine to treat anxiety, poor memory, and cognitive deficits. The beneficial effects of brahmi on the central nervous system may be mediated through its properties of increasing antioxidant enzyme (SOD, CAT, and GPx) activities. It is not known whether the immune-enhancing properties of brahmi are mediated through similar improvement in antioxidant enzyme status in the lymphoid organs. (Priyanka et al. 2013: 261)

Just now noticed (in Srimachai et al. 2017: 2) that antioxidant enzymes are myocardial, relating to the muscular tissue of the heart, though this attribution may originate from that study's focus on myocardial tissues. Evidently there are "antioxidannt enzyme activities" in a wide variety of cells.

Brahmi and donepezil had differential effects on the SOD and CAT activity but both increased the activities of GPx and GST. Similarly, both brahmi and donepezil selectively increased NO production and suppressed the extent of lipid peroxidation depending on the age groups. Both brahmi and donepezil increased P-ERK1/2 and p-CREB expression while brahmi alone increased p-Akt expression in the lymphocytes of early middle-aged and old rats. (Priyanka et al. 2013: 269)

The results show a pretty significant age-related variation, even reverse effects on specific antioxidant enzymes. Not sure yet what to make of this.

Brahmi (Bacopa monnieri Linn.) is widely used to improve learning and memory and also, reverse cognitive deficits associated with epilepsy but its effects on immune responses are not well known. Although bacoside, the active component of brahmi, was shown to enhance proliferation of T lymphocytes in vitro, there was no such effect on lymphocytic proliferation in the present study either in young, early middle-aged, or old rats. However, the in vitro treatment of lymphocites with brahmi, especially lower doses, enhanced IL-2 and IFN-γ production reversing the age-related suppression of cytokine production. (Priyanka et al. 2013: 269)

Much of this escapes my comprehension because I'm not at all at home in immunology. After this post I'm going to start with the earliest papers on BM and hopefully work myself up to an understanding of what is going on here.

The prevention of age-related decrease in NO production by brahmi in the present study indicates that it can influence immunity by causing vasodilation and trafficking of immune cells from spleen to other parts of the body. (Priyanka et al. 2013: 270)

When in doubt, fall back to vasodilation.

Parveen, Romana; Tooba Naz Shamsi, Humanshu Kumar and Sadaf Fatima 2016. Phytochemical analysis and in vitro biological characterization of aqueous and methanolic extract of Bacopa monnieri. International Journal of Pharmacy and Pharmaceutical Sciences 8(12): 90-96. DOI: 10.22159/ijpps.2016v8i12.14739

B. monnieri (Linn), commonly named as "Brahmi," belongs to the family Scrophulariaceae is an Indian valuable herb. It has been used in Ayurvedic system of medicine traditionally to treat conditions such as fever, inflammation, asthmma, epilepsy, pain and memory retardation (Gupta et al. 2014). (Parveen et al. 2016: 90)

There is something eerily suspicious about referring to biotechnologists with regard to the effects of the plant. I have a hunch that this is how the mythos of Brahmi is formed.

Some of the chemical elements of B. monnieri are lipophilic. This means that they can integrate with or dissolve in lipids providing them the ability to pass the blood-brain barrier (Mahato, Garain & Chakravarty 2000; Ramasamy, Kiew & Chung 2013). (Parveen et al. 2016: 90)

It'd be good to know which ones, though.

The phytochemicals such as betulinic acid, wogonin and oroxindin isolated from the aerial parts of B. monnieri showed aphoristic antifungal activity against Alternaria alternata and Fusarium fusiformis (Chaudhuri et al. 2004). (Parveen et al. 2016: 91)

Haven't even seen these mentioned thus far, though collection of papers shows another five papers mentioning wogonin and 3 mentioning oroxindin, including Chaudhari et al. (2017)

If there occurs any infection or damage to the body or tissue then body responds against the infection through inflammation. Protein denaturation is one of the major causes of inflammation. Due to this, we have tried to find out the ability of B. monnieri to inhibit protein denaturation. The results showed that BmAE and BmME were effective in inhibiting thermally induced albumin denaturation at different concentrations. (Parveen et al. 2016: 93)

Still learning basic biology from these papers.

Sharma, Munish; Ashok Ahuja, Rajinder Gupta and Sharada Mullabhotla 2015b. Enhanced bacoside production in shoot cultures of Bacopa monnieri under the influence of abiotic elicitors. Natural Product Research 29(8): 745-749. DOI: 10.1080/14786419.2014.986657

Bacopa monnieri (L.) Wettst. (Scrophulariaceae) commonly known as 'Brahmi' has played a very important role in Ayurvedic system of medicine as a memory enhancer as well as revitalizer of sensory organs, improving cognition and general neurological function (Kishore 2012). (Sharma et al. 2015b: 745)

It does what now to sensory organs?

Production of bacosides from plant tissue cultures is of immense importance as the drug content of the intact plant is very low, i.e. 0.2% (Tejavathi & SHailaja 1999 [Regeneration of plants from the cultures of Bacopa monnieri (L.) Pennell]. (Sharma et al. 2015b: 746)

The important secondary metabolites are basically the plant's immune system, as far as I can make out their native function.