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Maslinic acid alleviates ulcerative colitis by inhibiting the colitis-aggravating pathogen Clostridium perfringens and modulating gut microbiota

作者:Bailu Geng, Congmin Zhu, Zilu Cui, Yung‐Yi Chen, Qian Zhang, Haiyun Shi, Min Li, Shengtao Zhu, Weizhen Zhang, Mengran Zhao, Shutian Zhang, Junxuan Xu · 发表于:Phytomedicine · 年份:2025 · DOI:10.1016/j.phymed.2025.157144 · 被引用次数:11 · 研究领域:Inflammatory Bowel Disease、Gut microbiota and health、Natural product bioactivities and synthesis

BACKGROUND: Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease, continues to pose therapeutic challenges due to the limitations of conventional drugs and their inability to prevent relapse. Emerging evidence highlights the crucial role of gut microbiota dysbiosis in UC pathogenesis, yet our understanding of specific harmful microbes and their contributions to disease development remains limited. PURPOSE: This study aims to (1) investigate the therapeutic potential of maslinic acid (MA), a food-derived natural compound, in colitis mice models; (2) elucidate the previously underestimated pathogenic role of Clostridium perfringens in UC development; and (3) reveal the molecular mechanisms underlying both C. perfringens pathogenesis and MA-mediated protection. METHODS: We examined the therapeutic effect of MA using DSS-induced colitis model and performing metagenomic sequencing; elucidated the pathogenic role of C. perfringens using GMrepo database, clinical stool samples, and in vivo infection models. Additionally, we revealed its mechanism using inhibitors and markers of various cell death and inflammation pathways. The bactericidal effect of MA on C. perfringens was studied through in vitro experiments and two in vivo colitis models. RESULTS: MA alleviates DSS-induced colitis and restores gut microbiota. C. perfringens is enriched following DSS administration while significantly decreased after treatment with MA. C. perfringens contributes to the developme...