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Study Title:

Brain enhancing Bacopa monniera from Āyurvedic medicine

Study Abstract

Āyurveda, the science (ved) of life (ayu), owing its origin to Veda, the oldest recorded wisdom of human civilization written in 3500 BCE, contains extensive knowledge of various diseases and their therapeutic approaches. It essentially relied on nature and the immune system of an individual, and therapeutic interventions were introduced only to augment the immune system. Āyurveda had eight specialties, including psycho-neuroscience (a combination of psychology, clinical psychology and psychiatry) and a unique promotive therapy encompassing nutrition, rejuvenation and geriatrics. The symptoms of various brain disorders, including memory disorder, were well defined. The goal of Āyurveda was to help an individual to achieve his cherished goal of leading a healthy life of 100 years. To achieve this, great emphasis was laid on nutrition, diet and a good conduct by the two great exponents of Āyurveda viz. Carak and Suśruta. By following these regimens, an individual could lead a less stressful life free from emotional disturbances. Both Carak and Suśruta had believed that these in combination with rasayana (rejuvenating) plants could enable an individual to lead a healthy life of 100 years.

From Article:

We shall illustrate the unique properties of the rasāyanā plants by taking the example of Bacopa monniera. It is an extremely important plant of Āyurveda used since the time of Rig-Veda (c. 3500 BCE), and its name is derived from Lord Brahmā, the creator of universe in Hindu mythology and believed to be the originator of Āyurveda [27]. As has been shown in Table 1, Bacopa has been recommended in various Āyurvedic texts to be taken during each decade of life after the first decade. It has been classified as medhya-rasāyanā (memory enhancing and rejuvenating), as well as aindra-rasāyanā (increasing longevity and promoting progeny). Because of its traditional importance and unique traditional therapeutic claims of alleviating old age and age-related diseases, promoting memory and intellect, enhancing life-span, providing nourishment, excellence, clarity of voice, complexion and luster and being efficacious in a wide variety of psychiatric disorders, like hallucination, schizophrenia, obsessive compulsive disorder, severe psychosis and also producing a photographic memory, it has been investigated in different laboratories in India, particularly in the Central Drug Research Institute (CDRI), Lucknow. We will take the medhya-rasayana properties later. The aindra-rasāyanā effect has been negligibly investigated, except perhaps for a M.D. (Āyurveda) thesis by Diggavi [28]. The methodology used in the thesis is not very sound, chiefly because an unstandardized bacopa powder was administered to 10 patients randomly selected from the OPD of the Vājikarana (Sexology) section of the Kayāchikitsa department of Integrated Post-Graduate Teaching and Research in Āyurveda (IPGTRA) of Gujarat Āyurveda University, Jamnagar. All the patients were fulfilling the clinical Āyurvedic criteria of diagnosis of Klaibyā (Male Sexual Dysfunction). The total course of treatment was 30 days with 5g of bacopa powder three times a day with milk. The study was open-ended. Although increase in several parameters, including semen parameters, were observed, these were not significant. However, marked increase was observed with bacopa treatment on the sexual health in several parameters on an arbitrarily chosen subjective scale. Overall, bacopa treatment showed a varying degree of improvement in the volunteers (Figure 12).

Overall effect of bacopa treatment [28].

This aspects merits further investigation before the traditional claim of bacopa being an aindra-rasāyanā can be accepted scientifically.

However, because of the investigations done at CDRI, the traditional claim of bacopa being medhya-rasāyanā has been scientifically accepted.

A systematic chemical investigation of the plant by Basu et al. [29,30] and Chatterjee et al. [31] revealed that Bacopa contains the following constituents: Bacoside A (64.28%), Bacoside B (27.11%), betullic acid (4.58%), D-mannitol (0.83%), stigmasterol (0.54%), β-sitosterol (0.58%) and stigmastanol (2.08%). The activity of the ethanolic extract was traced to the mixture of the triterpenoid saponins designated as Bacosides A and B. Bacoside A is levo-rotatory and Bacoside B is dextro-rotatory.

Bacoside A was the major component of the plant and comprised two sets of saponins. One set was derived from pseudojujubogenin, which upon acid hydrolysis furnished four triterpenoid transformation products, viz. Bacogenins A1, A2, A3 and A4 [32]. The second set of saponins was derived from jujubogenin, which upon acid hydrolysis yielded two triterpenoids with triene side chains as transformation products. These triterpenoids were designated as Bacogenins A4 (trans) and (cis). A standardized extract of bacopa containing a minimum of 55% ± 5% of bacosides with an optimum concentration of Bacogenins (especially Bacogenin A4), vis-a-vis memory enhancing effect, was developed. This was termed as bacosides-enriched standardized extract of bacopa (BESEB CDRI-08).

To begin with, the BESEB CDRI-08 was tested in a critically selected learning model, which would produce well-distributed and extensive cellular changes during learning discrimination and involve a reversal of innate behavior. For instance, rodents being nocturnal animals prefer darkness in preference to light. If the learning model is such that an entry of the experimental animal in the lighted alley of the training maze escapes punishment and an entry in the dark alley is punished, then the model would serve the purpose of reversing the innate behavior of a preference of darkness. The model thus chosen was a foot-shock motivated brightness discrimination task on rats in a semi-automatic Y-maze described in detail by [33,34,35].

It is also important to use a battery of diversified tests whenever attempting to measure the effect of any drug on the level of motivation or emotion [36]. Hence, the memory enhancing effects of BESEB CDRI-08 were evaluated in a battery of tests consisting of positive (reward), as well as negative (punishment), reinforcements, on the labile phase of memory (when the memory is in formative stage) and stable phase of memory (when the memory formation has taken place). The training methods should also allow a clear demarcation of the three memory phases, viz. acquisition, consolidation and retention, and also clearly distinguish between the successive stages of short-term, intermediate and long-term memories. The foot-shock motivated brightness discrimination reaction fulfilled most of these criteria in as far as the training was completed in one session to produce a labile memory formation and it was with a negative reinforcement (punishment). However, to obtain predictive and confirmative evidence, the BESEB CDRI-08 was tested in other learning models of active avoidance response and Sidman’s continuous avoidance response (to produce a stable phase of memory with negative reinforcement in multi-session or interval sessions) and conditioned taste aversion response (to produce a labile phase of memory with positive reinforcement).

The result of these investigations confirmed that BESEB CDRI-08 has a significant facilitatory effect on all the forms of memory, i.e., short, intermediate and long-term memories in all the three phases, viz. acquisition, consolidation and retention [37,38,39,40,41,42,43,44].

Recent studies have shown that BESEB CCDRI-08 influenced the serotonergic system by elevating the level of 5-HT and up-regulating the expression of 5-HT3A receptor, possibly by interacting with the cholinergic system [38]. The improvement observed in the hippocampus-dependent learning model was possibly due to the combined effect of serotonergic and cholinergic systems. This is in conformity with other findings that multiple neurotransmitters are involved in the learning memory process [39,40,41,42,45,46,47,48,49].

BESEB CDRI-08 was found to be safe in regulatory sub-acute toxicity [50] and teratogenicity studies [51]. No abnormalities were observed in genotoxicity and mutagenicity [52]. The product was efficacious in the treatment of children suffering from attention deficit hyperactive disorder [53] and adults suffering from age-associated memory impairment [54,55,56] (Figure 13, Figure 14).

Effect of BESEB CDRI-08 (50 mg × 2 daily) on children suffering from attention deficit hyperactivity disorder.

Effect of BESEB CDRI-08 (150 mg × 2 daily) on elderly subjects suffering from age associated memory impairment.

BESEB CDRI-08 has shown its significant effectiveness in improving the cognitive symptoms associated with inattention, impulsiveness in children suffering from Attention Deficit Hyperactivity Disorder [53] and also showed significant improvement in several memory test scores on elderly subjects suffering from Age Associated Memory Impairment [54,55,56]. The extract has thus shown its putative potentials in the treatment of cognitive impairment. Considering its other interesting profile of activities, like anti-anxiety [17], the extract appears to be a potential treatment of the total loss of memory. Blood analysis would also be an important avenue for research on this extract, especially the identification of antioxidant markers.

Study Information

Singh HK.
Brain enhancing ingredients from Āyurvedic medicine: quintessential example of Bacopa monniera, a narrative review.
Nutrients.
2013 February
Lumen Research Foundation, Ashok Nagar, Chennai, India.