文献类型：期刊文献

英文题名：Coptidis rhizoma ameliorates type 2 diabetes mellitus-related metabolic dysfunction-associated steatohepatitis by downregulating the IL-17RA/NF-κB signaling pathway

作者：Yao, Ning[1];Wang, Xin[2];Chen, Yajie[2];Wu, Yunjuan[2];Su, Ying[2];Su, Xinxin[1];Geng, Yajuan[1];Liu, Xiaoning[3];Tian, Limin[4]

第一作者：姚凝

通信作者：Wang, X[1];Tian, LM[2]

机构：[1]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Coll Integrat Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[3]Lanzhou Univ, Sch Publ Hlth, Lanzhou, Gansu, Peoples R China;[4]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Endocrinol, Chengdu, Sichuan, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Coll Integrat Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Endocrinol, Chengdu, Sichuan, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：16

外文期刊名：FRONTIERS IN PHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-105018823237);WOS:【SCI-EXPANDED(收录号:WOS:001591422300001)】；

基金：The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. 82160845), the Natural Science Foundation of Gansu Province (No. 25JRRA254 and No. 20JR5RA181), the Traditional Chinese Medicine High Level Key Scientific Research Project of Gansu Province (No. GZKZ-2024-36), the Scientific Research Start-up Fund for Introduced Talent of Gansu University of Chinese Medicine (No. 2024YJRC-01), the Higher Education Innovation Foundation Project of Gansu Provincial Department of Education (2021B-173), and the Science and Technology Plan Project of Chengguan District, Lanzhou City, Gansu Province (No. 2021-2-5).

语种：英文

外文关键词：type 2 diabetes mellitus; metabolic dysfunction-associated steatohepatitis; Coptidis rhizoma; epiberberine; IL-17RA/NF-kappa B signaling pathway; traditional Chinese medicine

摘要：Background Coptidis rhizoma, a botanical drug derived from the dried rhizome of Coptis species (e.g., Coptis chinensis), is characterized by abundant natural sources, significant bioactivity, and high safety. It holds considerable potential for translational applications in metabolic diseases, particularly in ameliorating type 2 diabetes mellitus (T2DM)-related metabolic dysfunction-associated steatohepatitis (MASH). However, mechanistic studies on Coptidis rhizoma remain limited.Purpose This study aimed to evaluate the therapeutic effects of Coptidis rhizoma on hepatic histological and functional damage, metabolic disorders, and insulin resistance in T2DM-related MASH and investigate its underlying mechanisms.Methods Two-day-old male C57BL/6J mice were subcutaneously injected with streptozotocin (200 mu g/20 mu L per mouse). At 4 weeks of age, the mice were weaned and switched to a high-fat diet until week 9 to induce T2DM-related MASH. Starting from week 5, Coptidis rhizoma decoction was administered via oral gavage for four consecutive weeks to conduct in vivo studies. Additionally, hepatocytes were isolated from the model mice and exposed in vitro to epiberberine, the active metabolite of Coptidis rhizoma, for cellular-level investigations.Results Coptidis rhizoma significantly attenuated hepatic inflammatory lesions, reduced the non-alcoholic fatty liver disease activity score, improved liver function, and alleviated glucose and lipid metabolism disorders and insulin resistance in a dose-dependent manner in T2DM-related MASH mice. At the transcriptional level, key components of the interleukin-17 receptor A (IL-17RA)/nuclear factor kappa B (NF-kappa B) signaling pathway were upregulated in the hepatocytes of T2DM-related MASH mice, and both Coptidis rhizoma and epiberberine downregulated their expressions. Furthermore, Coptidis rhizoma and epiberberine suppressed the secretion of pro-inflammatory cytokines associated with the IL-17RA/NF-kappa B pathway in hepatocytes.Conclusion Coptidis rhizoma ameliorates pathological phenotypes in T2DM-related MASH by inhibiting the IL-17RA/NF-kappa B signaling pathway, and its active metabolite epiberberine is involved in mediating these protective effects.