biostudies-literatureQu CFundamental Research Funds for the Central UniversitiesGuangdong Basic and Applied Basic Research FoundationNational Natural Science Foundation of ChinaChina Postdoctoral Science FoundationGuangdong Provincial Administration of Traditional Chinese Medicine Research Project.39https://www.ebi.ac.uk/biostudies/studies/S-EPMC12805791biostudies-literatureUnknown21(1)Depression is a widespread mental disorder with profound effects on both physical and psychological health. Aberrant signal transduction contributes to depression by impairing neuronal function, reducing synaptic plasticity, and disrupting neurotransmitter transmission. Aberrant signal transduction can impair neuronal function, reduce synaptic plasticity, and disrupt neurotransmitter transmission, thereby contributing to the development of depression. Xiao-Yao-San (XYS), a traditional Chinese medicine (TCM) formula, has been extensively employed in the treatment of depression, with a broad therapeutic profile. This review aims to critically assess current scientific evidence on the antidepressant effects of XYS, focusing on its modulation of key signaling pathways. The goal is to provide aChinese medicineFrom classical Chinese formula to modern mechanism: how Xiao-Yao-San modulates key signaling pathways in depression.PMC12805791(No. 2023A1515110693; No. 2025A04J3396)(No.82430126)(No.20261072)(No. 2023M741396)(21624358).Qu CLiu YWang RChen JLiu AHao WZhao ZfalseFrom classical Chinese formula to modern mechanism: how Xiao-Yao-San modulates key signaling pathways in depression.Depression is a widespread mental disorder with profound effects on both physical and psychological health. Aberrant signal transduction contributes to depression by impairing neuronal function, reducing synaptic plasticity, and disrupting neurotransmitter transmission. Aberrant signal transduction can impair neuronal function, reduce synaptic plasticity, and disrupt neurotransmitter transmission, thereby contributing to the development of depression. Xiao-Yao-San (XYS), a traditional Chinese medicine (TCM) formula, has been extensively employed in the treatment of depression, with a broad therapeutic profile. This review aims to critically assess current scientific evidence on the antidepressant effects of XYS, focusing on its modulation of key signaling pathways. The goal is to provide a2026-01-01T00:00:00Z2026 Jan2026-06-06T15:41:55.82Z2026-06-02T03:08:51.391ZS-EPMC128057914153596710.1186/s13020-025-01315-7