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  2. Integrating 16S rDNA sequencing analysis and targeted metabolomics to explore the mechanism of Xiexin Tang in treating atherosclerosis mice induced by high-fat diet

Integrating 16S rDNA sequencing analysis and targeted metabolomics to explore the mechanism of Xiexin Tang in treating atherosclerosis mice induced by high-fat diet

  • J Pharm Biomed Anal. 2025 Jul 15:259:116760. doi: 10.1016/j.jpba.2025.116760.
Junling Li 1 Qianru Gao 1 Hongtao Liu 1 Songlin Liu 1 Yanchun Wang 1 Xiongjie Sun 1 Junping Zheng 1 Huabing Yang 2 Baifei Hu 3
Affiliations

Affiliations

  • 1 College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China.
  • 2 College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China. Electronic address: huabingyang@hbucm.edu.cn.
  • 3 College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Huangjiahu West Road 16, Wuhan 430065, PR China; Hubei Shizhen Laboratory, Huangjiahu West Road 16, Wuhan 430065, PR China. Electronic address: baifeihu@stmail.hbucm.edu.cn.
Abstract

Xiexin Tang (XXT) is a classic Chinese medicine formula that can be used to treat Atherosclerosis (AS). This study aimed to investigate the mechanism by which XXT regulated AS lipid levels. Firstly, the mixture components of XXT were analyzed by High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Then, the AS model based on Apolipoprotein E knockout (apoE-/-) mice was established. Cytokines related to lipid metabolism and bile acid metabolism were detected by Quantitative Real-Time PCR (qRT-PCR). 16S rDNA gene Sequencing was performed to analyze differential Bacterial populations, and the mechanism of XXT regulation of bile acids affecting lipid metabolism was further explored by targeted metabolomics. Further, antibiotic-treated mice were used to investigate the role of gut microbiota in the anti-AS effect of XXT. The results showed that XXT attenuated the lipid levels and reversed the abnormal elevation of cytokines, such as hepatic lipid metabolism and inflammatory reaction in AS mice. XXT also repaired the gut barrier damage and reversed gut microbiota disorders in AS mice. Furthermore, the metabolic levels of bile acids were reshaped by XXT. Whereas, in the absence of gut microbiota, XXT failed to attenuate lipid levels and inhibit the expression of cytokines related to inflammation and bile acid metabolism in AS mice and failed to play a role in ultimately treating AS. In conclusion, XXT could effectively inhibit the inflammatory reaction and lipid accumulation in AS mice, and this effect was closely related to its remodeling of gut microbiota to regulate bile acid metabolism.

Keywords

Atherosclerosis; Bile acid; Gut microbiota; Inflammation; Lipid metabolism; Xiexin tang.

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