Abstract | BACKGROUND: PURPOSE: To elucidate the underlying mechanisms of JTSH for treating T2DM with animal models. METHODS: In this study, male SD rats received high-fat diet (HFD) and streptozotocin (STZ) injection to induce T2DM and were treated with different dosages (0.27, 0.54 and 1.08 g/kg) of JTSH pill for 4 weeks; metformin was given as a positive control. Alterations of gut microbiota and BA profiles in the distal ileum were assessed by 16S ribosomal RNA gene sequencing and ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), respectively. Additionally, we conducted quantitative Real Time-PCR and western blotting to determine the mRNA and protein expression levels of intestinal farnesoid X receptor (FXR), fibroblast growth factor 15 (FGF15), Takeda G-protein-coupled receptor 5 (TGR5) and glucagon-like peptide 1 (GLP-1) as well as hepatic cytochrome P450, family 7, subfamily a, poly- peptide 1 (CYP7A1) and cytochrome P450, family 8, subfamily b, poly- peptide 1 ( CYP8B1), which are involved in BAs metabolism and enterohepatic circulation. RESULTS: Here, the results revealed that JTSH treatment significantly ameliorated hyperglycaemia, insulin resistance (IR), hyperlipidaemia, and pathological changes in the pancreas, liver, kidney and intestine and reduced the serum levels of pro-inflammatory cytokines in T2DM model rats. 16S rRNA sequencing and UPLC-MS/MS showed that JTSH treatment could modulate gut microbiota dysbiosis by preferentially increasing bacteria (e.g., Bacteroides, Lactobacillus, Bifidobacterium) with bile-salt hydrolase (BSH) activity, which might in turn lead to the accumulation of ileal unconjugated BAs (e.g., CDCA, DCA) and further upregulate the intestinal FXR/FGF15 and TGR5/ GLP-1 signaling pathways. CONCLUSION: The study demonstrated that JTSH treatment could alleviate T2DM by modulating the interaction between gut microbiota and BAs metabolism. These findings suggest that JTSH pill may serve as a promising oral therapeutic agent for T2DM.
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Authors | Dina Tawulie, Lulu Jin, Xin Shang, Yimei Li, Le Sun, Haixue Xie, Jie Zhao, Jiabao Liao, Zhangzhi Zhu, Huantian Cui, Weibo Wen |
Journal | Phytomedicine : international journal of phytotherapy and phytopharmacology
(Phytomedicine)
Vol. 113
Pg. 154733
(May 2023)
ISSN: 1618-095X [Electronic] Germany |
PMID | 36870307
(Publication Type: Journal Article)
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Copyright | Copyright © 2023 Elsevier GmbH. All rights reserved. |
Chemical References |
- San-Huang
- RNA, Ribosomal, 16S
- Bile Acids and Salts
- Cytochrome P-450 Enzyme System
- Glucagon-Like Peptide 1
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Topics |
- Rats
- Male
- Animals
- Gastrointestinal Microbiome
- Diabetes Mellitus, Type 2
(drug therapy, metabolism)
- Chromatography, Liquid
- RNA, Ribosomal, 16S
- Bile Acids and Salts
(metabolism)
- Rats, Sprague-Dawley
- Tandem Mass Spectrometry
- Liver
(metabolism)
- Cytochrome P-450 Enzyme System
(metabolism)
- Glucagon-Like Peptide 1
(metabolism)
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