Rong Ma, Junrui Ma, Hushan Zhang
Depression is a major global health concern, characterized by profound mental and physical debilitation that severely impairs quality of life. The World Health Organization projects that it will become the second-leading cause of global disease burden by 2030, underscoring the urgent need for effective therapeutic strategies. However, the pathogenesis of depression remains incompletely elucidated, and first-line pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs), are frequently limited by delayed clinical onset, suboptimal response rates, and notable adverse effects. In contrast, traditional Chinese medicine (TCM), with its holistic philosophy and potential for multi-target modulation, offers a promising complementary approach. This review systematically synthesizes contemporary research on TCM for depression, covering botanical drug formulas, single medicinal botanical drugs, and their purified bioactive metabolites. We critically evaluate the proposed mechanisms-spanning monoaminergic regulation, modulation of neurotrophic factors, anti-inflammatory activity, and interactions between the microbiota-gut-brain axis-and discuss the associated translational challenges and future research directions.