Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients.

Background: Depression is a severe mental disorder that poses a significant threat to both the physical and mental wellbeing of individuals. Currently, there are various methods for treating depression, including traditional Chinese herbal formulations like Chaihu-Shugan-San (CSS), which have shown effective antidepressant effects in both clinical and animal research. Objective: This review aims to provide a comprehensive synthesis of evidence related to CSS, considering both preclinical and clinical studies, to uncover its potential multi-level, multi-pathway, and multi-target mechanisms for treating depression and identify its active ingredients. Methods: A thorough search was conducted in electronic databases, including PubMed, MEDLINE, Web of Science, Google Scholar, CNKI, and Wanfang, using keywords such as "Chaihu Shugan" and "depression" to retrieve relevant literature on CSS and its active ingredients. The review process adhered to the PRISMA guidelines. Results: This review consolidates the mechanisms underlying antidepressant effects of CSS and its active ingredients. It emphasizes its involvement in the regulation of monoaminergic neurotransmitter systems, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis, among other aspects. Conclusion: CSS exerts a pivotal role in treating depression through various pathways, including the monoaminergic neurotransmitter system, the hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brain-derived neurotrophic factor levels, and the brain-gut axis. This review facilitates a comprehensive understanding of the current state of CSS research, fostering an in-depth exploration of the etiological mechanisms of depression and the potential discovery of novel antidepressant drugs.