BACOPA MONNIERI

Introduction

Bacopa monnieri (BM) is commonly called Brahmi in Ayurvedic medicine. Bacopa is an important ingredient in several Ayurvedic preparations, and is considered a Rasayana herb (rasa: primordial tissue or plasma; ayana: path), which are believed to prevent aging, re-establish youth, prevent disease, promote healthy longevity, and strengthen life, brain, and mind (1). Bacopa monnieri is a creeping perennial with small oblong leaves and purple flowers, found in warm wetlands, and native to Australia and India. Commonly found as a weed in rice fields, BM grows throughout East Asia and the United States. The entire plant is used medicinally. Unlike the potentially addictive and forceful action of widely used psychostimulants, chronic and moderate administration of BM appears to nourish rather than deplete neurons, an action compatible with 1400 years of Ayurvedic study. BM was initially described around the 6th century A.D. in texts such as the Charaka Samhita, Athar-Ved, and Susrutu Samhita as a medhya rasayana–class herb taken to sharpen intellect and attenuate mental deficits. The herb was allegedly used by ancient Vedic scholars to memorize lengthy sacred hymns and scriptures. In Australia, the Therapeutic Goods Administration regulates bacopa as an active ingredient of listed medicines with approved Ayurvedic use statements including “Bacopa monnieri has a tradition of use in Ayurvedic medicine for weakness of memory. It may help normal memory function.” (2)

The main nootropic constituents of BM are believed to be dammarane types of triterpenoid saponins known as bacosides, with jujubogenin or pseudo-jujubogenin moieties as aglycone units (3). Bacosides comprise a family of 12 known analogs (4). Novel saponins called bacopasides I–XII have been identified more recently (5-7).

 

Neuropharmacological Activity

Bacoside A administration increased the activities of superoxide dismutase (SOD), catalase, GPx, and GSR. As a result, the levels of glutathione (primary endogenous anti-oxidant conjugate) in the brain were significantly increased as well (8). In a related study, Anbarasi et al. (9) also showed that administration of bacoside A inhibited lipid peroxidation, improved the activities of adenosine triphosphatases (ATPases), and maintained ionic equilibrium in the brain. Rastogi et al. (10) examined the effect of long-term bacoside administration on age-associated neuroinflammation. The researchers found significant decreases in proinflammatory cytokines (interleukin-1b, tumor necrosis factor-a but not interferon-c), significant induction of inducible nitric oxide synthetase (iNOS) expression, and significant reduction of total nitrite and lipofuscin content in the cortex.

Kamkaew et al. (11) compared the effect of daily oral BM and Gingko biloba on cerebral blood flow (CBF). In their 8-week trial, those treated with BM saw a significant 25% increase in CBF, although Gingko biloba increased CBF by 29%.

 

Adaptogenic effects

Adaptogens enable the body to better cope with the deleterious mental and physical consequences of stress. Eleutherococcus senticosus (Siberian ginseng), Rhodiola rosea, and Panax ginseng are classic adaptogens. Others include Ocimum sanctum (Sweet Holy Basil or Tulsi), Withania somnifera (Ashwaghanda), Astragalus propinquus, Ganoderma lucidum (Reishi mushroom), and many others (12). BM also exhibits adaptogenic qualities. One putative action of the adaptogen is modulation of neurotransmitter (NT) production, release, and synaptic concentration. Sheikh et al. (13) evaluated BM’s adaptogenic effect in acute stress and chronic unpredictable stress-induced fluctuations of plasma corticosterone and monoamines. Treatment with BM attenuated stress-induced changes in levels of 5-HT and dopamine (DA) in the cortex and hippocampus. In the chronic stress model, pretreatment with BM significantly elevated levels of nor-adrenaline (NA), DA, and 5-HT in the cortex and NA and 5-HT in the hippocampus compared to controls. Prevention of NT depletion is the cornerstone of adaptogenic stamina enhancement, both physical and mental.

 

Neuroprotection

Mathew and Subramanian (14) examined the effect of BM extract on free b-amyloid aggregation in vitro using fluorescence imaging. They compared a whole plant BM methanol extract to 12 other herb extracts, finding several to prevent aggregation of b-amyloid plaques and to dissociate pre-formed fibrils. Incubating with BM extract was found to ‘‘almost completely’’ inhibit b-amyloid formation.

Dhanasekaran et al. (15) demonstrated that an ethanol extract of BM exhibited neuroprotective effects. BM reduced divalent metals, dose-dependently scavenged ROS, decreased the formation of lipid peroxides, and inhibited lipoxygenase activity in vitro.

In another study, some of the same researchers found that BM reduced b-amyloid plaques in an Alzheimer model by up to 60% (16). A comprehensive in vitro study by Limpeanchob et al. (17) found BM to protect against β amyloid-induced (but not glutamate-induced neurotoxicity. The mechanism was attributed to greater anti-oxidant activity and AChE inhibition in the BM group.

 

Memory

Most of the recent clinical studies on bacopa investigated its effect on cognition, memory, anxiety, and/or depression in healthy volunteers (either elderly or of unspecified age) or in Alzheimer’s patients. In one 2011 open-label, prospective, uncontrolled, non-randomized study, 39 Alzheimer’s patients (60-65 years) were given alcohol extract standardized to bacopa glycosides) twice daily for 6 months (18). Patients showed significant improvements in various areas, including attention, orientation of person, place, and time, and in reading, writing and comprehension.

A randomized, double-blind, placebo-controlled (RDBPC) study in 2010 investigated bacopa’s efficacy in improving memory performance in older healthy people (19). Ninety-eight participants over 55 years of age were randomized to receive 300 mg/day bacopa or placebo for 12 weeks. The bacopa group showed significantly improved memory acquisition and retention.

Although BM clinical research is in its infancy, at least six high-quality (by the Jadad Scale (20) randomized, doubleblind, placebo-controlled (RDBPC) human trials have been conducted. Pase et al. (21) conducted a systematic review, finding some evidence that ‘‘Bacopa could potentially be clinically prescribed as a memory enhancer’’ even in non-demented subjects. BM administration significantly improved 9 out of 17 free recall memory tasks. One out of six of the studies’ collective scores evidenced improved memory span. The analysis of Pace et al. supports previous findings that BM most effectively reduces the rate of forgetting, but not acquisition or other aspects of cognition (though this matter is by no means settled).

 

Nootropic effects

In a meta-analysis, Neale et al. (22) compared the nootropic effects of BM to Panax ginseng and modafinil (an eugeroic wakefulness drug). Chronic BM produced the most consistent and largest effect sizes of the three. BM showed small- to medium-effect sizes for attention and information processing tasks. Larger-effect sizes were evident for auditory verbal learning tasks, sizes ranging from d = 0.23 for delayed word pair memory to d = 0.95 for delayed word recall (on the Auditory Verbal Learning Test) and d = 1.01 for protection from proactive interference during delayed memory. These findings evidence the potency of BM, particularly in measures of verbal recall. Remarkably, contemporary findings appear to support the alleged use of BM in Vedic antiquity by scholars memorizing lengthy hymns.

Some of the clinical studies described in detail in Pase et al. will be summarized here. All subjects were administered BM orally. Stough et al. (23) conducted a (RDBPC) study in 46 healthy adults (300 mg/day standardized to 55% bacosides) for 12 weeks. A battery of eight tests was taken, finding significantly improved speed of visual information processing, learning rate, memory consolidation, and state anxiety compared to placebo, with maximal effects evident after 12 weeks.

Morgan and Stevens (24) conducted a DBRPC trial with 81 elderly Australians, finding highly significant improvements in verbal learning, memory acquisition and delayed recall. Nathan et al. (25) conducted a RDBPC trial using a single administration of extract with testing 2 hr post-administration. The researchers found no significant acute cognitive effect in the BM group. The absence of noticeable acute effects may diminish the likelihood of dependency-forming or -reinforcing behaviour.

 

Cognitive function

In 2008, Calabrese et al. studied the effects of a whole plant standardized dry extract of bacopa on cognitive function and safety (26). In a RDBPC trial, each of 48 healthy participants, 65 years or older (mean 73.5 years), who completed the study were given either once daily bacopa extract or placebo for 12 weeks. Over the course of the study, the bacopa group had improved delayed recall memory and Stroop task reaction times, while the placebo group experienced no change. The bacopa group also experienced decreased depression and anxiety while the placebo recipients increased in both. In another 2008 RDBPC study, 62 healthy volunteers were given either a dry extract standardized to bacosides or placebo daily for 90 days (27). Participants underwent a cognitive assessment at baseline and at the end of the study. The bacopa group experienced significantly improved performance in spatial working memory accuracy. Roodenrys et al. (2002) conducted a RDBPC study to test the effect of bacopa on anxiety and various memory functions (28). Of the 76 healthy participants who completed the study (28 males and 48 females between 40 and 65 years of age), 37 were given bacopa extract and 39 were given placebo. Participants were tested before the trial began, at 6 weeks, and after the trial ended. Preliminary tests showed no differences between the groups but the active group experienced improved retention of new information in recall of word pairs in later testing. The authors posited that it was the antioxidant effect of bacopa on the hippocampus that was responsible for the improved retention.

 

References

1. Puri HS. Rasayana; Ayruvedic Herbs for Longevity and Rejuvenation. London: Taylor and Francis, Inc.; 2003.

2. Therapeutic Goods Administration. October 2001. Guidelines for Kinds and Levels of Evidence to Support Indications and Claims for Non-registerable Medicines including Complementary Medicines, and other Listable Medicines, Version 1.1. Woden, Australia: Australian Government Department of Health and Ageing Therapeutic Goods Administration. April 2011. Available at: www.tga.gov.au/pdf/cm-evidence-claims.pdf.

3. Sivaramakrishna C, Rao CV, Trimurtulu G, Vanisree M, Subbaraju GV. Triterpenoid glycosides from Bacopa monnieri. Phytochemistry 2005;66:2719–2728.

4. Garai S, Mahato SB, Ohtani K, Yamasaki K. Dammarane triterpenoid saponins from Bacopa monnieri. Can J Chem 2009;87:1230–1234.

5. Chakravarty AK, Sarkar T, Masuda K, Shiojima K, Nakane T, Kawahara N. Bacopaside I and II: two pseudojujubogenin pseudojujubogenin glycosides from Bacopa monniera. Phytochemistry 2001;58:553–556.

6. Chakravarty A.K, Garai S., Masuda K, Nakane T, Kawahara N. Bacopasides III–V: Three new triterpenoid glycosides from Bacopa monniera. Chem Pharm Bull 2003;51:215–217.

7. Garai S, Mahato SB, Ohtani K, Yamasaki K. Dammaranetype triterpenoid saponins from Bacopa monniera. Phytochemistry 1996 42:815–820.

8. Anbarasi K, Vani G, Balakrishna K, Devi CS. Effect of bacoside- A on brain antioxidant status in cigarette smoke exposed rats. Life Sci 2006;78:1378–1384.

9. Anbarasi K, Vani G, Balakrishna K, Devi CS. Effect of bacoside-A on membrane-bound ATPases in the brain of rats exposed to cigarette smoke. J Biochem Mol Toxicol 2005;19: 59–65

10. Rastogi M, Ojha R, Prabu PC, Devi DP, Agrawal A, Dubey GP. Amelioration of age associated neuroinflammation on long term bacosides treatment. Neurochem Res 2012;37: 869–874.

11. Kamkaew N, Scholfield N, Ingkaninan K, Taepavarapruk N and Chootip K. Bacopa monnieri increases cerebral blood flow in rat independent of blood pressure. Phytother Res 2013;27:135–138.

12. Winston D, Maimes S. Adaptogens: Herbs for Strength, Stamina, and Stress Relief. Healing Arts Press, 2007.

13. Sheikh N, Ahmad A, Siripurapu KB, Kuchibhotla VK, Singh S, Palit G. Effect of Bacopa monniera on stress induced changes in plasma corticosterone and brain monoamines in rats. J Ethnopharmacol 2007;111:671–676.

14. Mathew M, Subramanian M. Evaluation of the anti-amyloidogenic potential of nootropic herbal extracts in vitro. IJPSR 2012;3:4276–4280.

15. Dhanasekaran M, Tharakan B, Holcomb LA, Hitt AR, Young KA, Manyam BV. Neuroprotective mechanisms of ayurvedic antidementia botanical Bacopa monniera. Phytother Res 2007;21:965–969.

16. Holcomb LA, Dhanasekaran M, Hitt AR, Young KA, Riggs M, Manyam BV. Bacopa monniera extract reduces amyloid levels in PSAPP mice. J Alzheimer’s Dis. 2006;9:243–251.

17. Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K. Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol 2008;30;120:112–117.

18. Goswami S, Saoji A, Kuman N, Thawani V, Tiwari M, Thawani M. Effect of Bacopa monnieri on cognitive functions in Alzheimer’s disease patients. International Journal of Collaborative Research on Internal Medicine & Public Health. 2011;3(3):179.

19. Pravina K, Ravindra KR, Goudar KS, et al. Safety evaluation of BacoMind™ in healthy volunteers: a phase I study. Phytomedicine. 2007;14:301-308.

20. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reportsvof randomized clinical trials: Is blinding necessary? Control Clin Trials 1996;17:1–12.

21. Pase MP, Kean J, Sarris J, Neale C, Scholey AB, Stough C. The cognitive-enhancing effects of Bacopa monnieri: A systematic review of randomized, controlled human clinical trials. J Altern Complement Med 2012;18:1–6.

22. Neale C, Camfield D, Reay J, Stough C, Scholey A. Cognitive effects of two nutraceuticals Ginseng and Bacopa benchmarked against modafinil: A review and comparison of effect sizes. Br J Clin Pharmacol 2012; online publication.

23. Stough C, Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, Nathan PJ. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology 2001;156:481–484.

24. Morgan A, Stevens J. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med 2010;16:753–759.

25. Nathan PJ, Clarke J, Lloyd J, Hutchison CW, Downey L, Stough C. The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects. Hum Psychopharmacol 2001;16:345–351.

26. Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, Oken B. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial. J Alt Comp Med. 2008;14(6):707-713.

27. Stough C, Downey LA Lloyd J, et al. Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial. Phytotherapy Res. December 2008;22(12):1629-1634.

28. Roodenrys S, Booth D, Bulzomi S, et al. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology. 2002;27(2):279-281.