文献类型：期刊文献

英文题名：Study on the mechanism of modified Gegen Qinlian decoction in regulating the intestinal flora-bile acid-TGR5 axis for the treatment of type 2 diabetes mellitus based on macro genome sequencing and targeted metabonomics integration

作者：Liu, Rong[1,2,3];Wang, Jiahui[2];Zhao, Yikun[2];Zhou, Qi[2];Yang, Xia[2];Gao, Yankui[2];Li, Qin[2,4];Bai, Min[2];Liu, Jiahui[3];Liang, Yonglin[2,3];Zhu, Xiangdong[5]

第一作者：Liu, Rong;刘润;刘茹

通信作者：Liang, YL[1];Zhu, XD[2]

机构：[1]Jiangxi Univ Chinese Med, Nanchang 330004, Jiangxi, Peoples R China;[2]Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China;[3]Res Ctr Tradit Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[4]Gansu Hlth Vocat Coll, Lanzhou 730000, Gansu, Peoples R China;[5]Ningxia Med Univ, 1160 Shengli St, Yinchuan 750004, Ningxia Hui, Peoples R China

第一机构：Jiangxi Univ Chinese Med, Nanchang 330004, Jiangxi, Peoples R China

通信机构：[1]corresponding author), Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Ningxia Med Univ, 1160 Shengli St, Yinchuan 750004, Ningxia Hui, Peoples R China.|[10735]甘肃中医药大学;

年份：2024

卷号：132

外文期刊名：PHYTOMEDICINE

收录：;Scopus(收录号：2-s2.0-85195261118);WOS:【SCI-EXPANDED(收录号:WOS:001255629600001)】；

基金：This work was supported by the Industry Support Plan Project of Gansu Provincial Department of Education (2021CYZC-03) , Open Project of Research Center of Traditional Chinese Medicine, Gansu Province (zyzx-2023-07) , Key R & D Plan Project of Ningxia Hui Autonomous Region (2022CMG02034) , Innovation Star Project for Excellent Graduate Students of Gansu Province (2022CXZX-734) , Key Laboratory of Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University and Ningxia Regional Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Regional High Incidence Disease, Ningxia Medical University.

语种：英文

外文关键词：Modified Gegen Qinlian decoction; Intestinal flora-bile acid-TGR5 axis; Type 2 diabetes; Macro genome sequencing; Targeted metabonomics

摘要：Background: Currently, there are many drugs available for the treatment of type 2 diabetes mellitus (T2DM), but most of them cause various side effects due to the need for long-term use. As a traditional Chinese medicine, Gegen Qinlian Decoction (GQD) has shown good efficacy and low side effects in the treatment of T2DM in both clinical and basic research. Based on relevant traditional Chinese medicine theories, dried ginger is innovatively added the formula of traditional GQD to create a modified GQD. This modification reduces the side effects of traditional GQD while exerting its therapeutic effect on T2DM. Previous studies have found that the modified GQD can regulate endoplasmic reticulum stress in the liver, inhibit hepatic gluconeogenesis, protect pancreatic islet beta cells, and control blood sugar levels by inhibiting the FXR/neuronal ceramide signaling pathway. GQD can also regulate the intestinal microbiota to achieve therapeutic and protective effects in various gastrointestinal diseases. However, there is no research exploring whether the modified GQD achieves its therapeutic mechanism for T2DM by regulating the intestinal microbiota. Purpose: To explore the mechanism of modified GQD in the treatment of T2DM based on multi-omics, focusing on its effect on the " intestinal flora bile acid TGR5 ' ' axis. Methods: The T2DM model was established using db/db mice, which were randomly divided into a model group, metformin group, high-dose GQD group, medium-dose GQD group, low-dose GQD group, while m/m mice were used as blank control. The drug intervention lasted for 12 weeks, during which the general conditions, oral glucose tolerance (OGT), blood glucose, and lipid-related indexes were recorded. Additionally, the fasting insulin (FINS), c-peptide, GLP-1 in serum, and cAMP in the ileum were measured by ELISA assay. Furthermore, the composition, abundance, and function of the intestinal microbiota were determined by macro genome sequencing, while bile acid was detected by targeted metabonomics. For histological evaluation, HE staining was used to observe the pathological changes of the ileum and pancreas, and the ultrastructure of the ileum and pancreas was observed by transmission electron microscopy. Apoptosis in the ileum tissue was detected by Tunel staining. Moreover, the mRNA and protein expressions of TGR5, PKA, CREB, PC1/3, GLP-1, and their phosphorylation levels in the ileum were detected by qPCR, immunohistochemistry, and Western blot; The expression of INS in the pancreas was also evaluated using immunohistochemistry. Finally, double immunofluorescence staining was used to detect the co -localization expression of TGR5 and GLP-1, NeuroD1, and GLP-1 in the ileum. Results: The modified GQD was found to significantly reduce blood glucose, improve oral glucose tolerance, and blood lipid levels, as well as alleviate the injury of the ileum and pancreas in T2DM mice. Furthermore, modified GQD was found to effectively regulate intestinal flora, improve bile acid metabolism, activate the TRG5/cAMP/ PKA/CREB signal pathway, and stimulate GLP-1 secretion. Conclusion: GQD can regulate the "intestinal flora -bile acid-TGR5" axis and has a therapeutic effect on T2DM in mice.