From Ayurvedic Wisdom to Potential Modern-Day Medicine

Traditional use of Bacopa in Ayurveda

Bacopa (Bacopa monnieri) – otherwise known as ‘Brahmi’ in Ayurveda – is a small creeping herb that belongs to the Scrophulariaceae family. Highly valued for nearly 3000 years in its native country of India, Bacopa is described as medhya-rasāyanā (memory enhancing and rejuvenating), as well as aindra-rasāyanā (increasing longevity).^1-4 Apart from being an important brain tonic in Ayurvedic medicine, Bacopa is also considered a reputable nerve tonic that is used to treat anxiety, nervous exhaustion and debility, as well as a trusted cardiotonic,^5-7 making it an ideal remedy for the more mature patient.

Scientific Investigation and The Increasing Prevalence of Dementia

Due to its popularity as a cognitive enhancing (nootropic) agent, Bacopa has increasingly attracted the attention of the scientific community. Fuelling this interest is a global shift towards an aging population and therefore an increasing prevalence of various forms of dementia, often preceded by mild cognitive impairment (MCI).

According to Dementia Australia, people with MCI are 3-5 times more likely to develop dementia than their peers - especially Alzheimer’s Disease (AD).⁸ Without a medical breakthrough, dementia cases in Australia are expected to rise to 900,000 by the year 2050.⁹ Worldwide, around 42% of the world population over the age of 60 suffer MCI.¹⁰

Figure 1. ‘Hypothetical model for the pathological – clinical continuum of Alzheimer’s Disease’: Lundbeck Institute.⁴⁰

Unfortunately, there is no specific treatment for MCI to date.⁸ However, some herbal medicines have been reported to improve cognitive function in those with mild memory impairment. One such herb is Bacopa, which has been investigated in numerous studies, including human clinical trials, where it was shown to exert various actions that lead to the amelioration of cognitive dysfunction, as well as cognitive enhancement in healthy people.

Noteworthy is that some bacopa extracts have shown to improve cognitive function while others have not. Studies that used specific bacopa extracts however, clearly demonstrate statistically significant benefits,² such as those using the proprietary extract BacoMind®, which is standardised to provide 40-50% bacosides from nine active constituents: bacoside A3, bacopaside I, bacopaside II, jujubogenin isomer of bacopasaponin C, bacosine, luteolin, apigenin, and b-sitosterol-D-glucoside.¹¹

In an Australian randomised controlled clinical trial (RCT) in 98 healthy participants, daily administration of 300 mg of BacoMind® was shown to be effective in enhancing memory performance in healthy people over the age of 55 years, with improvements observed in both memory acquisition and retention.¹² In another RCT in elderly individuals from India, BacoMind® given at a dose of 450 mg once daily for 12 weeks also improved cognitive parameters, such as attention and verbal memory.¹³ 

Overall, studies on Bacopa used 200 to 600 mg of extract standardised to 40-55% bacosides per day for a duration of 12 weeks in healthy subjects or subjects with MCI.¹⁴

Mechanisms of Action

The main neurological pathways involved in memory and cognition include the cholinergic, dopaminergic, and serotoninergic pathways, as well as inflammatory and neuroprotective or antioxidant pathways.^2,3,15 Bacopa has been shown to affect all of the above pathways, as well as other molecular targets that affect cognition (see table below), with the saponin bacosides A and B considered the most active constituents responsible.³

Bioactive components of Bacopa monnieri2 Various saponins have been identified, specifically those known as bacopasides I-XII. Other components include apigenin, cucurbitacin, alkaloids brahmine, monnierin, hersaponin, monnierasides I-III, plantain side B, d-mannitol, herpestine, and nicotine, as well as betulinic acid, wogonin, and oroxindin. The pharmacological activities of bacopa are attributed to the saponin bacoside and bacopasaponin constituents.2

Effects of Bacopa on various neurological pathways and molecular targets that affect cognition 

Cholinergic pathway	Bacopa modulates the release of acetylcholine, as well as the activity of choline acetylase and muscarinic cholinergic receptor binding, therefore improving speed of information processing.3,15 Bacopa inhibits Prolyl endopeptidase (PEP) which degrades the neuropeptides arginine-vasopressin, oxytocin, neurotensin and substance-P, all of which strongly influence learning and memory processes.2,18 In vitro studies have shown that Bacopa is able to inhibit acetylcholinesterase2 (a mechanism that is characteristic of AD drugs).
Dopaminergic pathway	Bacopa modulates memory functions by inhibiting the enzyme catechol-O-methyl transferase (COMT), an enzyme that is involved in dopamine metabolism and signalling.16
Serotonergic pathway	Bacopa has an antagonistic effect on serotonin 6 and 2A (5-HT and 5-HT) receptors known to influence different neurological pathways associated with memory and learning. Down-regulation of these serotoninergic targets have been shown to improve memory.18
GABA pathway	Bacopa increased cerebral levels of gamma-aminobutyric acid (GABA),2 i.e. via its PEP-inhibiting activity.
Neuroprotective or antioxidant pathway	Bacopa helps to repair damaged neurons, promotes neuronal synthesis and restores restoration of synaptic activity.16 The high ORAC value of Bacopa is responsible for its neuroprotective activity, especially in brain areas responsible for memory function. Bacopa directly scavenges free radicals, but also stimulates endogenous antioxidant systems. More specifically, Bacopa inhibits the enzyme poly (ADP-ribose) polymerase (PARP), which suggests a reduction in secondary oxidative damage.2,3,18
Anti-inflammatory pathway	Bacopa inhibits inflammation by inhibiting the release of prostaglandin E2, histamine, serotonin and bradykinin. It also ihibits cyclooxygenase -2, 5-lipoxygenase (5-LOX) and 15-LOX, and downregulates tumor-necrosis factor-alpha (TNF),3  especially in the inflamed brain.17

Figure 2: Cognitive Effects of Bacopa Monnieri.¹⁸

Complementary Herbs and Nutrients to Support Cognition

There are numerous herbs and nutrients that have been found to support brain health and cognition in those suffering from MCI, but also help with associated conditions such as mood changes and depression, which commonly occur in these patients.¹⁹

Active Ingredient	Therapeutic Effects
Saffron (Crocus sativa) stigma	Saffron was shown to improve cognitive ability and disease progression compared to placebo in patients with probable AD when taken over 16 weeks at a dose of 15 mg twice daily.20 The same dose of Saffron taken for 22 weeks demonstrated comparable cognitive and clinical outcomes in adults 55 years and older who presented with dementia and probable Alzheimer's disease when compared to those who received conventional therapy with donepezil (Aricept).21 Saffron acts as a potent antioxidant.22 Numerous meta-analyses and systematic reviews confirm that Saffron is effective in treating mild-to-moderate depression.23-28
Acetyl-L-Carnitine (ACL)	According to a meta-analysis of 12 RCTs, 1.5 to 3 g per day of ACL taken for 3-12 months improves MCI or prevents cognitive deterioration.29
Zinc	Zinc concentration in the brain are 10 times higher than levels found in serum.30 Zinc helps to enhance memory and improves mental development via its function as a neuronal messenger and modulator of synaptic transmission and plasticity.31,32
Tyrosine	Tyrosine has been shown to improve measures of cognitive performance,33-35 and to improve memory under stressful conditions.36,37 Tyrosine may play a role in depression, due to its role as a precursor for the neurotransmitters of catecholamines, norepinephrine, epinephrine, and dopamine.38,39

References

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