Recently, Professor Jiaxu Chen's team from the School of Traditional Chinese Medicine at Jinan University and the Guangzhou Key Laboratory of Syndrome and Formula Research of Traditional Chinese Medicine, with support from the National Natural Science Foundation of China, the Key Research and Development Program of Guangdong Province, and the Guangdong Basic and Applied Basic Research Foundation, has revealed new mechanisms of action of the traditional Chinese medicine formula XIAOYAO SAN in combating depression. The findings were published in Microbiome.
Depression is a major global mental disorder and falls within the scope of traditional Chinese medicine's concept of "yu zheng." XIAOYAO SAN, originating from the Song Dynasty official pharmacopeia Tai Ping Hui Min He Ji Ju Fang, is a classic formula known for its effects of soothing the liver, relieving depression, invigorating the spleen, and nourishing the blood. However, its mechanism of action has remained unclear. Dysregulation of gut microbiota-mediated activation of peripheral and prefrontal cortical complement C3 in microglial cell abnormalities is an important pathogenic mechanism of depression and a potential mechanism of action of the traditional Chinese medicine formula XIAOYAO SAN.
Utilizing germ-free animal models combined with fecal microbiota transplantation and metabolomics detection, the study found that dysregulation of gut microbiota-driven peripheral and prefrontal cortical complement C3-mediated microglial abnormal synaptic pruning is one of the key pathogenic mechanisms of depression. Moreover, XIAOYAO SAN and fecal microbiota transplantation after XIAOYAO SAN treatment improved depression-like behavior in model mice, indicating that XIAOYAO SAN exerts its antidepressant effects in a gut microbiota-dependent manner. Its mechanism is related to regulating gut microbiota dysbiosis, inhibiting microbiota-driven peripheral and central prefrontal cortical complement C3 activation, and improving microglial-mediated abnormal synaptic pruning.
The study, starting from the perspective of traditional Chinese medicine formula regulating the intestinal environment, systematically elucidated the mechanism by which XIAOYAO SAN improves depression-like behavior through modulating the "gut-brain" axis, providing new insights into the mechanism research of traditional Chinese medicine formulas.
Additionally, the team led by Professor Chen discovered that 18β-glycyrrhetinic acid (18β-GA), a key component of XIAOYAO SAN entering the brain, confirmed that the activation of BDNF transcription in the prefrontal cortex is the basis of the antidepressant effect of 18β-GA, and 18β-GA is a key component formed by the metabolism of XIAOYAO SAN in the body. The relevant findings were published in Phytomedicine.
Related paper information: https://doi.org/10.1186/s40168-024-01756-6
