HighlightsBacopa monnieri is a creeping plant considered in the Ayurvedic system as a herb to boost memory [3].Brahmi contains Bacosides which are a family of saponins with unique neuroprotective and adaptogenic effects on the CNS [5,7].Brahmi has double-blind, randomized, placebo- controlled studies in humans demonstrating its nootropic and adaptogenic effects [1,2,3,4,5].BackgroundBacopa monnieri, otherwise known as Brahmi, is a creeping plant inhabiting marshy areas, and is considered in the Indian Ayurvedic system of medicine as a “memory booster herb” [3]. Constituent analysis of Brahmi shows that most of its activity is derived from the presence of alkaloids and triterpenoids [3] – more specifically the family of saponins known as Bacosides A and B, which encompass at least 12 purified compounds so far [7]. There is some evidence to suggest that extracts of Brahmi may be beneficial in improving cognitive function in the attention domain, especially speed of attention [4], learning, and memory with chronic administration [6]. Research into the mechanism of action for the effects of Brahmi has shown cholinergic, antioxidant, and adaptogenic effects in the central nervous system [5].Brahmi’s traditional use as a memory booster is bolstered by modern studies, many of which are randomized double-blind placebo-controlled trials which substantiate the memory boosting and nootropic effects of Brahmi [1, 4, 5], especially in older populations which are particularly sensitive to neurological conditions ranging from mild memory loss to Alzheimer’s Disease.Mode of actionAlthough the mechanisms for Brahmi’s neuroprotective and nootropic effects have not yet been fully elucidated. With over 12 unique steroidal saponins [7] and at least 8 other pharmacological constituents including alkaloids and alcohols [3], the exact mode of action is complex and varies based on dosage and chronic administration.The first mode of action by which Brahmi works isthrough its antioxidant activity, which has been shown to upregulate expression of various antioxidant molecules such as SOD and glutathione, as well as quenching hydrogen peroxide-mediated oxidative stress both in-vitro and in-vivo [3]. Another study which examined rat brains treated with Brahmi extracts showed a significant regression of Heat-shock protein 70 (Hsp70) in rats given stress after treatment, which may hint at Brahmi’s localized effectiveness in the hippocampus [2] and also has implications for the reduction of protein aggregation in the brain duet alpha-synuclein [1]. It was also seen that treatment with the Brahmi extracts modulated the activity of the P450 enzymes [2], which are known to be involved in ROS scavenging, however further research needs to be performed to elucidate the role of these enzymes in relation to Brahmi’s mode of action. It was also seen in rats that administration of intravenous backside A inhibited lipid peroxidation, improved the activities of ATPases, and maintained ionic equilibrium (including zinc and selenium) in brans of cigarette smoke-exposed rats [1]. Brahmi was also found in rat models to increase the Nrf2 and Nf-kappa β transcription factors [3], which are two major transcription factors involved in the antioxidant machinery of cells. In addition, the Brahmi extract in itself has shown radical scavenging potential and reduction of nitrogen radicals in vitro [1, 3].Brahmi also has neuroprotective effects, especially against inflammation in diseases such as Alzheimer’s. For instance, even lower doses of Brahmi extract treatment (in vitro) were found to reduce the interleukin and TNF-α levels in microglial cells which are part of the known immunological pathways involved in Alzheimer’s Disease [3]. In rat models of Alzheimer’s, Brahmi was found to reverse memory impairment, reduce lipid per- oxidation and protein carbonyl levels, and also restore the activity of some anti-oxidant enzymes [1]. In aged rat brains, Brahmi also restored acetylcholine levels and monoamine levels to concentrations seen in young rats, which elucidates that one of the mechanisms of Brahmi is through choline acetyltransferase activation rather than acetylcholine esterase inhibition [1]. This study not only showed that potentiation of monoamine and 5-HTP were through a non-obvious cellular mechanism, but also that there was a mild antidepressant effect associated with this mechanism in rats [1]. It was also found that one of the bioactive components of Brahmi, Betulinic acid, reduced pro-inflammatory responses in cell lines by reducing the COX-2 expression and prostaglandin E2 pro- duction, as well as attenuating the Akt and ERK signaling cascades [3]. Through similar neuroprotective and anti-inflammatory mechanisms, there is also similar pre- clinical evidence suggesting that Brahmi could be useful in treating Parkinson’s Disease [1, 3]. As with Ashwagandha, Brahmi has also been found to inhibit Amyloid- β-mediated toxicity associated with Alzheimer’s [3]. One of the key differences between Ashwagandha and Brahmi is that one of the bioactive components of Brahmi, Baco- side A, directly dissolves the matured Amyloid-β aggregates in cells, and has limited evidence suggesting that it can cross the blood-brain barrier in mouse models [3].Pharmacological effectsBrahmi has multiple effects which are mainly anti-inflammatory, antioxidant, adaptogenic, and nootropic [5], which lend the Ayurvedic herb to a few different uses.Brahmi has been shown in double-blind, placebo- controlled, randomized human trials to improve memory with results comparable to modafinil [1, 6]. Researchers also found that although Brahmi did not improve the rate of learning, that the rate of forgetting was significantly attenuated in word-pair trails after 3 months of chronic use [1, 5]. Increased verbal recall was also noted, which supports the alleged use of Brahmi in Vedic antiquity by scholars memorizing lengthy rhythms [1]. This also means that Brahmi has potential for positive pharmacological effects in those suffering from neurodegenerative disorders, especially as an agent for mild improvements in cognitive behavior in both animal and human studies [3].As an apoptogenic compound, there is evidence present in rat models that Brahmi is able to reduce the amount of stress-related compounds produced and has good potential to allow for better brain function under adverse stress events [2]. Additionally, Brahmi has been shown to protect against neuroinflammation and regulate cell metabolism which could be useful pharmacological effects against neurodegenerative diseases [3].Potential useAs described above, Brahmi has complex mechanisms of action which ultimately lead to its popular use in adaptogenic and nootropic applications— hence its popularity as a “memory booster” herb [3].Most of Brahmi’s activity is derived from the presence of alkaloids, triterpenoids, and saponins known as Bacosides [3], of which over 12 different kinds exist [7]. Thus its potential use can vary, however, the most vet- ted and researched usage, both in animal trials and randomized double-blind placebo-controlled trials, is as an anti-inflammatory and nootropic [1, 4, 5]. This makes it a potential medicine to be used in conjunction with traditional medicines for neurodegenerative diseases such as Alzheimer’s or amnesia [1, 5].More research still needs to be done in terms of the consistency of pharmacological constituents, effects of different Bacosides, and mitigation of negative intestinal side effects before Brahmi can become widely used in mainstream medicine [1, 3, 5].References[1] C. Aguiar and T. Borowski. Neuropharmacological review of the nootropic herb bacopa monnieri. RE- JUVENATION RESEARCH, 16(4):313–325, 2013.[2] D.K. Chowdhuri, D. Parmar, P. Kakkar, R. Shukla, P. K. Seth, and R. C. Srimal. Antistress effects of bacosides of bacopa monnieri: modulation of hsp70 expression, superoxide dismutase and cytochrome p450 activity in rat brain. Phytotherapy Research, 16(7):639–645, 2002.[3] T. Dubey and S. Chinnathambi. Brahmi (bacopa monnieri): An ayurvedic herb against the Alzheimer's disease. Archives of Biochemistry and Biophysics, 676:108153, 2019.[4] C. Kongkeaw, P. Dilokthornsakul, P. Thanarangsarit, N. Limpeanchob, and N. Scholfield. Meta-analysis of randomized controlled trials on cognitive effects of bacopa monnieri extract. Journal of Ethnopharmacology, 151(1):528–535, 2014.[5] A. Morgan and J. Stevens. Does bacopa monnieri improve memory performance in older persons? results of a randomized, placebo-controlled, double-blind trial. The Journal of Alternative and Complementary Medicine, 16(7):753–759, 2010. PMID: 20590480.[6] C. Neale, D. Camfield, J. Reay, C. Stough, and A. Scholey. Cognitive effects of two nutraceuticals ginseng.
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