The zhuyu pill relieves rat cholestasis by regulating the mRNA expression of lipid and bile metabolism associated genes

Frontiers in Pharmacology

Pharmacology

Huan Tao¹  Xinglong Liu²  Xiaodan Zhang²  Qiaobo Ye²  Chao Liu²  Fenghua Zhang²  Han Yu²  Xiaofeng Chen²  Jun Han²  Tao Shen²  Peijie Wu²  Yueqiang Wen³ 

[1] Department of Dermatology, Cangxi Traditional Chinese Medicine Hospital, Guangyuan, China;School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China;School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China;Department of Pediatrics, Guang’an Traditional Chinese Medicine Hospital, Guang’an, China;

关键词: cholestasis;    interventional mechanism;    bile metabolism;    lipid metabolism;    zhuyu pill;   

DOI  :  10.3389/fphar.2023.1280864

 received in 2023-08-21, accepted in 2023-09-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: The Zhuyu pill (ZYP), composed of Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, is an effective traditional Chinese medicine with potential anti-cholestatic effects. However, the underlying mechanisms of ZYP remain unknown.Objective: To investigate the mechanism underlying the interventional effect of ZYP on mRNA-seq analysis in cholestasis rat models.Materials and methods: This study tested the effects of a low-dose (0.6 g/kg) and high-dose (1.2 g/kg) of ZYP on a cholestasis rat model induced by α-naphthyl-isothiocyanate (ANIT, 50 mg/kg). Serum biochemistry and histopathology results were used to evaluate the therapeutic effect of ZYP, and mRNA-Seq analysis was performed and verified using real-time fluorescence quantitative PCR (qRT-PCR). GO, KEGG, and GSEA analyses were integrated to identify the mechanism by which ZYP impacted cholestatic rats.Results: ZYP was shown to significantly improve abnormal changes in the biochemical blood indexes and liver histopathology of cholestasis rats and regulate pathways related to bile and lipid metabolism, including fatty acid metabolism, retinol metabolism, and steroid hormone biosynthesis, to alleviate inflammation, cholestasis, and lipid metabolism disorders. Relative expression of the essential genes Cyp2a1, Ephx2, Acox2, Cyp1a2, Cyp2c11, and Sult2a1 was verified by qRT-PCR and showed the same trend as mRNA-seq analysis.Conclusion: ZYP has a significant anti-cholestatic effect by regulating bile metabolism and lipid metabolism related pathways. These findings indicate that ZYP is a novel and promising prospect for treating cholestasis.

【 授权许可】

Unknown   
Copyright © 2023 Han, Wu, Wen, Liu, Liu, Tao, Zhang, Zhang, Ye, Shen, Chen and Yu.