Assessment of Anxiolytic Activity of Brahmi (<i>Bacopa monnieri</i>) in Zebrafish Model System

Abstract

The increasing prevalence of anxiety and stress-related disorders has made it a leading contributor to the global health burden. The present treatment options have severe side effects and show remission on discontinuation of the medication. Hence, there is an urgent need to explore safer alternative treatments for long-term usage with minimum toxicity. The medicinal plant Brahmi (Bacopa monnieri) has been used in Indian traditional medicine as a neural tonic for centuries. The present study aimed to study the toxicity and anxiolytic activity of Brahmi using the zebrafish model system. The toxicity assays determined the minimum effective concentration of Brahmi to be 0.01%. In addition, behavioral assays such as thigmotaxis and scototaxis and endocrine assays such as the measurement of cortisol levels in stressed zebrafish larvae were performed. Zebrafish embryos exposed to 0.2% Brahmi up to seven days post fertilization (dpf) did not show any developmental toxicity. Behavioral and endocrine assays were performed on 5dpf zebrafish larvae treated with 0.01% Brahmi extract. Our studies show that Brahmi significantly reduced thigmotaxis (wall hugging) and scototaxis behavior in zebrafish larvae exposed to osmotic stress as compared to untreated stressed larvae. Stress activates the hypothalamic-pituitary-interrenal axis and stimulates the release of cortisol in zebrafish larvae. Whole body cortisol assay has shown that Brahmi significantly reduced the stress-induced release of cortisol in zebrafish larvae. Our studies report that Brahmi mitigates the stress response in zebrafish larvae and has minimum toxicity. This suggests that Brahmi may be a safe option for long term management of stress.