Co-administration of berberine and evodiamine: Mitigating evodiamine-induced hepatotoxicity and potentiating colitis treatment

作者：Xiaoyu Tao, Yifei Gao, Zhengsen Jin, Shan Lu, Zhiqi Li, Siyu Guo, Qiqi Fan, Jiaqi Li, Chuanqi Qiao, Huiling Lei, Zhiqiang Zhang, Chongjun Zhao, Jiarui Wu · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.157185 · 被引用次数：5 · 研究领域：Berberine and alkaloids research、Quinazolinone synthesis and applications、Phytochemistry and biological activities of Ficus species

BACKGROUND: The combined therapeutic mechanisms of evodiamine (EVO) and berberine (BBR), which are the primary bioactive components contributing to the pharmacological effects of Euodiae Fructus and Rhizoma Coptidis, a classic herb pair used for colitis, have not yet been fully elucidated PURPOSE: This study aimed to investigate the critical mechanisms by which co-administration EVO and BBR mitigated EVO-induced hepatotoxicity while exerting therapeutic effects against colitis. METHODS: Safety and therapeutic outcomes of EVO alone and combined BBR were validated in normal and colitis models. RNA-seq sequencing was performed on liver and colon tissues from different groups, while metagenomic sequencing was utilized to analysis fecal samples. An integrated bioinformatics analysis of transcriptomic and metagenomic data was conducted to reveal the mechanisms underlying EVO-induced hepatotoxicity and the protective and synergistic effects of BBR against colitis. Molecular biology experiments were employed to validate the regulatory mechanism, with a particular emphasis on the interactions within the gut- liver axis, including those related to lipid metabolism and inflammatory pathways. RESULTS: BBR attenuated EVO-induced hepatotoxicity in C57 mice by ameliorating pathological injuries and hepatic steatosis as well as inhibiting abnormal AST/ALT elevation, thereby revealing its hepatoprotective effects. In colitis mice, the combination therapy exhibited enhanced efficacy in reducin...