Investigation of the therapeutic effect of Yinchen Wuling Powder on CCl4-induced hepatic fibrosis in rats by 1H NMR and MS-based metabolomics analysis
Investigation of the therapeutic effect of Yinchen Wuling Powder on CCl4-induced hepatic fibrosis in rats by 1H NMR and MS-based metabolomics analysis
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DOI：
10.1016/j.jpba.2021.114073
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发表时间：
2021-04-17
影响因子：
3.4
通讯作者：
Wang，Miao
中科院分区：
文献类型：
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作者：
Zhang，Yumeng;Zhao，Min;Wang，Miao
肝纤维化（HF）是各种慢性肝病的典型后果，目前尚无理想的治疗药物。茵陈五苓散是著名的中药方剂，临床上对黄疸型肝炎、肝纤维化、非酒精性脂肪肝等肝病有较好的治疗作用，但其治疗肝纤维化的机制尚不清楚。本研究通过沿着大鼠体重变化、血清肝功能指标、血清肝纤维化指标及肝组织病理学观察，结合1H NMR和MS代谢组学分析，评价YCWLP对肝纤维化的治疗作用及其机制。药效学研究结果表明，养肝丸颗粒对肝纤维化有明显的治疗作用。在代谢组学研究中，由于YCWLP对CCl4诱导的肝纤维化的保护作用，血浆样品中有7种代谢物、尿液样品中有28种代谢物和肝脏样品中有6种代谢物发生了显著改变。这些内源性代谢产物参与氨基酸代谢、碳水化合物代谢、甘油磷脂代谢和肠道细菌代谢。提示养肝丸颗粒可能通过促进尿素循环、减少血氨蓄积、改善糖代谢、减轻氧化应激、改善甘油磷脂代谢、保护细胞膜、调节肠道植物群代谢等途径治疗肝纤维化。
Hepatic fibrosis (HF) is a typical consequence of various chronic liver diseases, and there is still no ideal drug for its treatment. Yinchen Wuling Powder (YCWLP), a famous traditional Chinese medicine prescription, is effective for the treatment of icteric hepatitis, hepatic fibrosis, non-alcoholic fatty liver disease and other liver diseases in clinical practices, however, the underlying mechanisms of YCWLP on HF is still unclear. In this study,1H NMR and MS-based metabolomics analysis along with body weight change, serum liver function indexes, serum liver fibrosis index and histopathological observations of liver were applied to evaluate the therapeutic effect of YCWLP on hepatic fibrosis and the mechanism associated with this. The results of the pharmacodynamics study show that YCWLP has a significant therapeutic effect on hepatic fibrosis. As for the metabolomics research, 7 metabolites in the plasma samples, 28 in the urine samples and 6 in the liver samples were significantly altered due to the protective effect of YCWLP on CCl4-induced hepatic fibrosis. These endogenous metabolites are involved in amino acid metabolism, carbohydrate metabolism, glycerophospholipid metabolism and gut bacteria metabolism. These findings suggest that YCWLP could treat hepatic fibrosis by promoting urea circulation and reducing blood ammonia accumulation, improving carbohydrate metabolism and reducing oxidative stress, improving glycerophospholipid metabolism and protecting cell membrane, and regulating intestinal flora metabolism.