Berberine: An isoquinoline alkaloid targeting the oxidative stress and gut-brain axis in the models of depression

Depression seriously affects people's quality of life, and there is an urgent need to find novel drugs to cure treatment-resistant depression. Berberine (BBR), extracted from Coptis chinensis Franch., Phellodendron bark, Berberis vulgaris, and Berberis petiolaris, could be a potential multi-target drug for depression. To summarize the effects of BBR on depression in terms of in vitro or in vivo experiments, we searched electronic databases, such as PubMed, Web of Science, Google Scholar, Wanfang Database, and China National Knowledge Infrastructure, from inception until May 2024. Then, we summarize that BBR has indirect antidepressant properties to improve depressive symptoms, manifesting in modulating the gut microbial community, strengthening the intestinal barrier, increasing the abundance of short-chain fatty acid-producing bacteria, and regulating tryptophan metabolism. BBR also exerts antidepressant-like effects via remodulating nuclear factor-erythroid 2-related factor 2/antioxidant response element pathway, hypothalamic-pituitary-adrenal axis, and peroxisome proliferators-activated receptor-delta. Nevertheless, further clinical trials and more high-quality animal studies are needed to show the actual clinical value of BBR for depression.