Bacopa: Therapeutic Potential for Alzheimer’s Disease?

In Ayurvedic medicine, bacopa (Bacopa monnieri, Plantaginaceae) is called brahmi and used as a brain tonic to enhance cognitive function and prevent memory loss. Bacopa monnieri extract (BME) has antioxidant and neuroprotective properties and, in clinical studies, has been found to improve aspects of cognitive function and memory in both healthy participants and patients with cognitive impairments. The purpose of this literature review was to summarize the experimental and clinical evidence supporting the therapeutic potential of BME for Alzheimer’s disease (AD). Various formulations of BME were used in the studies reviewed by the authors.

Mechanisms of Action

In animal and cell studies, BME has been shown to decrease oxidative stress by inhibiting lipid peroxidation, scavenging free radicals, inhibiting the generation of reactive oxygen species (ROSs), and upregulating antioxidant enzymes, among numerous other mechanisms. BME also has been found to ameliorate mitochondrial and plasma membrane damage, protect against cytotoxicity and inhibit necrotic changes and aggregation of lipofuscin (a pigment associated with cell aging) in rat brains.

In vitro, BME also has been found to enhance the synthesis of acetylcholine, increase acetylcholine concentrations, decrease acetylcholinesterase (AChE) activity, and modulate the metabolism of monoaminergic neurotransmitters. In rats with induced cognitive impairment, BME appeared to have a significantly greater effect when combined with the AChE inhibitor rivastigmine.

BME protected neurons in vitro from amyloid-beta (Ab)-induced cytotoxicity, and bacoside A (a group of chemicals from bacopa) significantly inhibited Ab-induced cytotoxicity, fibrillation, and Ab membrane interactions. In rodent models of AD, BME has been shown to improve learning and memory, improve cognitive ability and anti-amnesic activity in aged mice, reverse retrograde and anterograde amnesia, increase discrimination of new objects, and improve spatial learning in amnesiac mice.

In rats, BME has been shown to downregulate the expression of intestinal P-glycoprotein and liver cytochrome P450 3A enzymes, which regulate the absorption and metabolism of many drugs. This suggests a potential for herb-drug interactions, but the clinical significance is unknown.

Human Clinical Studies

The authors briefly describe 15 clinical trials, including 12 double-blind, placebo-controlled (DBPC) studies in adults, one placebo-controlled study in healthy children, one open-label study in children requiring educational support, and one open-label study in participants with AD. The number of participants was only reported for some of the studies; based on the data provided, sample sizes ranged from 17 to 98 participants. BME doses ranged from 150 mg/d to 640 mg/d, with 300 mg/d used in seven studies. One study evaluated a combination product that contained 320 mg BME, 30 mg saffron (Crocus sativus, Iridaceae) stigma, vitamins, and minerals. Although all of the studies assessed various aspects of cognitive function, such as attention, learning, and memory, the results cannot be directly compared due to the high degree of heterogeneity among the outcome measures.

In 40 healthy children (6-8 years old) treated with one teaspoon of bacopa syrup (equivalent to 350 mg of “crude Brahmi”) or placebo three times daily for three months, no improvements were observed in the placebo group, while the bacopa syrup treatment group had strengthened exploratory drive, improved perceptual images of patterns, and increased perceptual organization and reasoning ability. In an open-label study, children requiring individual educational support who were treated with 225 mg/day BME for 16 weeks experienced significant improvements compared to baseline in working memory, spatial working memory, short-term verbal memory, logical memory, visual memory, and auditory memory.

Most of the DBPC trials enrolled healthy middle-aged and elderly adults. All of the studies reported improvement in various aspects of cognitive function, most commonly heterogeneous measures of memory function, learning, attention, and speed of processing. The study that assessed the cognitive effects of acute doses in 17 young adults (mean age of 25 years) one and two hours after ingestion found significant improvements in information processing speed at both time points.

Only one trial evaluated patients with AD. The open-label study evaluated BME for six months in 39 patients (60-65 years old), and improvements were observed in some aspects of the Mini-Mental State Exam, including orientation, attention, and language comprehension.

The AD open-label study and 10 of the DBPC trials assessed CDRI-08, a bacoside-enriched standardized BME originally developed by the Central Drug Research Institute in Lucknow, India (produced under license by M/s Pharmanza Herbal Pvt. Ltd. [Gujarat, India] and sold under various trade names) or a comparable standardized BME. In these studies, 300-600 mg/d for 12-24 weeks significantly enhanced some aspects of cognitive performance in healthy participants, elderly people, and patients with AD.

Conclusion

Although the clinical studies are heterogeneous, it appears that BME improves some aspects of cognition in healthy participants and is a promising candidate to help some symptoms of AD. However, well-designed DBPC trials are lacking. In addition, because some of the experimental evidence suggests the cognitive effects of BME are dose-dependent, studies also are needed to determine the optimum dose for AD patients. Limitations of this narrative literature review include the lack of a comprehensive literature search and missing information in several of the clinical studies. In addition, the methodological quality of the clinical studies was not assessed, safety was not reported, and the sample sizes were relatively small.

Reviewed: Abdul Manap AS, Vijayabalan S, Madhavan P, et al. Bacopa monnieri, a neuroprotective lead in Alzheimer [sic] disease: A review on its properties, mechanisms of action, and preclinical and clinical studies. Drug Target Insights. 2019;13:1-13. DOI: 10.1177/1177392819866412.

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