Sini San ameliorates symptoms of depression by modulating gut microbiota structure, Tryptophan metabolism, and short-chain fatty acid levels

作者：Liangting Zhu, Junjie Hu, Juan Li, Xinyue Qu, Xian Zhou, Guoping Gan, Yanwen Liu, Songlin Liu, Xin Chen · 发表于：BMC Complementary Medicine and Therapies · 年份：2025 · DOI：10.1186/s12906-025-05190-5 · 被引用次数：3 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Treatment of Major Depression

BACKGROUND: Sini San (SNS) is a traditional Chinese medicinal formulation originating from the "Treatise on Febrile Diseases", an ancient text that has been historically employed for treating depression. However, the underlying mechanisms by which SNS potentially ameliorates symptoms of depression remain unclear. This study aimed to elucidate the role of gut microbiota in tryptophan metabolism and examine the involvement of short-chain fatty acids (SCFAs) in the putative antidepressant effects of SNS. METHODS: A rat model of depression using chronic unpredictable mild stress (CUMS) was established through simultaneous modeling and treatment for six consecutive weeks. The possible therapeutic effect of SNS on CUMS-induced rats was thoroughly assessed using body weight measurements, open-field tests, and sucrose preference tests. Alterations in rat gut microbiota were analyzed using full-length 16 S rRNA third-generation sequencing. Furthermore, metabolomic analysis was performed on fecal samples. An enzyme-linked immunosorbent assay (ELISA) was used to quantify tryptophan (Trp), serotonin (5-HT), and kynurenine (Kyn) in the hippocampal and colonic tissues. Reverse transcription quantitative PCR (RT-qPCR) was used to measure the mRNA levels of TPH-1 and TPH-2 in hippocampal and colonic tissues. Immunofluorescence was used to assess hippocampal IDO-1 and IBA-1 expression. Finally, gas chromatography-mass spectrometry (GC-MS) was used to analyze the SCFAs content in fecal samples...