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四氯化碳致肝纤维化的代谢谱变化及加芪肝纤颗粒的抑制作用

Metabolic Profile Changes of CCl₄-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule.

作者信息

Wang Ge, Li Zehao, Li Hao, Li Lidan, Li Jian, Yu Changyuan

机构信息

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing 100029, China.

出版信息

Molecules. 2016 May 30;21(6):698. doi: 10.3390/molecules21060698.

Abstract

Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry (UPLC-TOF-MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from a carbon tetrachloride (CCl₄)-induced hepatic fibrosis model in Sprague-Dawley (SD) rats with JGG treatment. Through Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA), it was shown that metabolic perturbations induced by CCl₄ were inhibited after treatment of JGG, for 17 different metabolites related to CCl₄. Among these compounds, the change tendency of eight potential drug targets was restored after the intervention with JGG. The current study indicates that JGG has a significant anti-fibrosis effect on CCl₄-induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, while glycerophospholipid metabolism played vital roles in the inhibitory effects of JGG on hepatic fibrosis according to Metabolic Pathway Analysis (MetPA). Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional Chinese medicine.

摘要

加芪肝纤颗粒(JGG)是一种著名的传统中药,长期以来一直用于临床治疗肝纤维化。然而,其抗肝纤维化的机制仍不清楚。在本研究中,采用基于超高效液相色谱-飞行时间质谱(UPLC-TOF-MS)的代谢组学策略,对用JGG治疗的四氯化碳(CCl₄)诱导的Sprague-Dawley(SD)大鼠肝纤维化模型血清的代谢特征进行分析。通过主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)表明,JGG治疗后,CCl₄诱导的代谢紊乱受到抑制,与CCl₄相关的17种不同代谢物发生了变化。在这些化合物中,8种潜在药物靶点的变化趋势在JGG干预后得以恢复。本研究表明,JGG对CCl₄诱导的大鼠肝纤维化具有显著的抗纤维化作用,其机制可能是通过调节鞘脂代谢、甘油磷脂代谢、N-酰基乙醇胺生物合成、脂肪消化和吸收的功能障碍,而根据代谢途径分析(MetPA),甘油磷脂代谢在JGG对肝纤维化的抑制作用中起重要作用。我们的研究结果表明,代谢组学方法可能为探索参与肝纤维化的潜在生物标志物以及阐明中药治疗作用的机制提供一个有用的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5a9/6273034/64518cf09106/molecules-21-00698-g001.jpg

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