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

机译:CCl4-肝纤维化的代谢谱变化及加气肝纤颗粒的抑制作用

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摘要

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. View Full-Text
机译:佳奇肝仙颗粒(JGG)是一种著名的中药,在临床上已被广泛用于治疗肝纤维化。但是,其抗肝纤维化的机制尚不清楚。在这项研究中,基于超高效液相色谱-飞行时间质谱(UPLC-TOF-MS)的代谢组学策略用于分析从四氯化碳(CCl4)诱导的肝纤维化获得的血清的代谢特征JGG处理的Sprague-Dawley(SD)大鼠模型。通过主成分分析(PCA)和偏最小二乘判别分析(PLS-DA),发现JGG处理后CCl4诱导的代谢扰动被17种与CCl4相关的代谢物所抑制。在这些化合物中,JGG干预后恢复了八个潜在药物靶标的变化趋势。目前的研究表明,JGG对CCl4诱导的大鼠肝纤维化具有明显的抗纤维化作用,这可能是通过调节鞘脂代谢,糖脂代谢,N-酰基乙醇胺的生物合成,脂肪的消化和吸收的功能障碍,而糖脂代谢发挥的作用。根据代谢途径分析(MetPA),在JGG抑制肝纤维化中起重要作用。我们的研究结果表明,代谢组学方法可能为探索与肝纤维化有关的潜在生物标志物提供有用的工具,并阐明中药治疗作用的潜在机制。查看全文

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