School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China; Department of Pharmacy, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China.
Biochem Biophys Res Commun. 2024 Feb 5;695:149411. doi: 10.1016/j.bbrc.2023.149411. Epub 2023 Dec 19.
Berberine, isolated from Coptis chinensis and Phellodendron amurense, can attenuate colonic injury and modulate gut microbiota disorders in ulcerative colitis (UC). However, the mechanism and causal relationship between gut microbiota and the efficacy of Berberine on UC are still unclear, which were investigated by pseudo-germ-free (PGF) mice, 16S rRNA gene analysis and transcriptome analysis in this study. The results demonstrated that Berberine improved gut microbiota disorders, colon damage, tight-junction proteins, inflammatory and anti-inflammatory cytokines in DSS-induced colitis mice with intact gut microbiota but not in PGF mice. Besides, immune-related and inflammation-related pathways were closely related to the efficacy that Berberine alleviated colitis by regulating gut microbiota. Furthermore, Berberine reduced PGE2, PLA2, COX-2, Ptges, EP2 and p-Stat3 only in colitis mice with intact gut microbiota. In summary, our study confirms that Berberine inhibits PLA2-COX-2-PGE2-EP2 pathway in UC through gut microbiota, leading to the alleviation of inflammation in colon, which further elucidates the underlying mechanism and promotes the application of Berberine in UC.
小檗碱来源于黄连和黄皮树，可减轻溃疡性结肠炎（UC）的结肠损伤并调节肠道微生物群紊乱。然而，肠道微生物群与小檗碱对 UC 的疗效之间的机制和因果关系仍不清楚，本研究通过无菌（PGF）小鼠、16S rRNA 基因分析和转录组分析对此进行了研究。结果表明，小檗碱改善了肠道微生物群紊乱、结肠损伤、紧密连接蛋白、炎症和抗炎细胞因子，在具有完整肠道微生物群的 DSS 诱导的结肠炎小鼠中，但在 PGF 小鼠中没有。此外，免疫相关和炎症相关途径与小檗碱通过调节肠道微生物群缓解结肠炎的疗效密切相关。此外，小檗碱仅在具有完整肠道微生物群的结肠炎小鼠中降低 PGE2、PLA2、COX-2、Ptges、EP2 和 p-Stat3。总之，我们的研究证实，小檗碱通过肠道微生物群抑制 UC 中的 PLA2-COX-2-PGE2-EP2 途径，从而减轻结肠炎症，进一步阐明了其潜在机制，并促进了小檗碱在 UC 中的应用。
