Review of Bacopa for the Treatment of Alzheimer’s Disease

Bacopa (Bacopa monnieri, Plantaginaceae) aerial plant extract is also known as Brahmi in India. The plant grows six inches to three feet tall near freshwater aquatic sites and has oblong leaves and purple flowers. The entire plant and roots are used medicinally. In Ayurvedic medicine, bacopa is used for memory improvement (decreasing forgetfulness, not increasing learning), epilepsy, insomnia, and anxiety. Saponins (bacoside A, bacoside B, bacopa saponins, D-mannitol, acid A, and monnierin) are the main constituents responsible for the pharmacological actions. Bacopa has antioxidant, anti-inflammatory, anticonvulsant, cardiotonic, bronchodilator, and peptic ulcer protection activity. The purpose of this article was to review studies evaluating bacopa for treating Alzheimer’s disease (AD). Bacopa has a good safety profile and may be effective for AD because of its antioxidant, cholinergic, and anti-beta-amyloid activity.

The brain is susceptible to free radical damage, which results in aging and cognitive decline. Many in vitro and in vivo studies demonstrate that bacopa has antioxidant and free radical scavenging activity; inhibits lipid peroxidation in the prefrontal cortex, hippocampus, and striatum of rats; and inhibits hydrogen peroxide-induced lipid peroxidation in mouse brain. Moreover, in vivo studies demonstrate that bacopa has a role in (1) improving brain plasticity via altering brain-derived neurotrophic factor (BDNF), (2) improving cerebral blood flow, which enhances cognitive function in rats, and (3) reducing amyloidogenic proteins in mice brains.

The literature search method was not described. The author’s highlight five “major” in vivo studies that evaluated bacopa for AD. (1) Cold stress in vivo decreased the size of hippocampal cells and decreased cell packing density in a histophotometric study. The effect of cold stress was reversed to near normal in rats treated with bacopa. (2) Rats treated with bacopa for eight weeks had cerebral blood flow increase by 25% and improved cognitive function. (3) Bacopa decreased cognitive dysfunction in olfactory bulbectomized mice by enhancing synaptic plasticity-related signaling and preserving cholinergic neurons. The mice had improved object recognition, spatial memory, and fear-induced long-term memory deficit. (4) Mice treated with bacopa had reduced oxidative damage caused by 3-nitropropionic acid (3-NPA). (5) Mice brain exposed to bacopa had decreased lipoxygenase activity, decreased hydrogen peroxide-induced lipid peroxidation, and inhibited iron chelation.

The authors highlight three “major” human studies that evaluated bacopa for AD, but they provide only a very brief description of each study. (1) In a double-blind, randomized, placebo-controlled study conducted in Lucknow, India, subjects (n = 35, aged > 55 years) were treated with bacopa (dose and product not reported) or placebo for 12 weeks. Subjects were evaluated with the Wechsler Memory Scale. The bacopa-treated subjects had a significant improvement in total memory score compared with placebo-treated subjects (P value not reported). The greatest improvement was in the logical memory subscale. The authors conclude that this study suggests that bacopa “can be [a] useful agent in the treatment of age-associated memory impairment.” (2) In a randomized, double-blind, placebo-controlled study conducted in Australia, subjects (n = 81, aged > 55 years) were treated with 300 mg/day bacopa (product not reported) or placebo for 12 weeks. “[R]emarkable improvement was demonstrated in verbal learning, memory acquisition, and delayed recall.” (3) In a double-blind, randomized, placebo-controlled study, healthy adults (n = 76) were treated with 300 mg/day bacopa (product not reported) or placebo for 12 weeks. Attention, memory, and psychological state were assessed. There was an increase in information retaining capacity over time, which was attributed to decreased forgetfulness. Bacopa had no beneficial effect on learning assessments.

Bacopa extract can be administered in the three following forms: Brahmi Ghritam (clarified butter-based oral supplement), Churna (powder), or tablets/capsules. To treat AD, the authors report the use of 250-500 mg of bacopa capsules one or two times per day, or Brahmi Churna or Ghritam 1-2 g, one or two times per day (references for these doses are not given).

Most of the bacopa safety data are from animal studies, although two clinical studies have reported adverse effects (AEs) data. One clinical trial in healthy men reported no significant AEs with 20-200 mg bacopa. In the second clinical trial, with subjects > 55 years treated with 300 mg/day for 12 weeks, the most common AEs were nausea, gastrointestinal upset, and intestinal hypermotility. The authors note that additional safety studies in humans are needed.

The authors conclude that large, multicenter, clinical trials are needed to confirm the safety and efficacy of bacopa in the treatment of AD. It is stated that there was no funding source and the authors declare no conflict of interest.

Source:

Chaudhari KS, Tiwari NR, Tiwari RR, Sharma RS. Neurocognitive effect of nootropic drug Brahmi (Bacopa monnieri) in Alzheimer’s disease. Ann Neurosci. 2017;24(2):111-122.

Advertisements