The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai, China.
Laboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
J Nutr Biochem. 2022 Aug;106:109020. doi: 10.1016/j.jnutbio.2022.109020. Epub 2022 Apr 25.
Nonalcoholic steatohepatitis, one of the most common chronic liver diseases, is a progressive form of nonalcoholic fatty liver disease accompanied by the development of liver fibrosis. Chlorogenic acid (CGA) is a natural polyphenolic compound. This study aims to observe the CGA-provided alleviation on liver fibrosis in methionine and choline deficient (MCD) diet-induced nonalcoholic steatohepatitis in mice and to elucidate its engaged mechanism. CGA attenuated hepatocellular injury, decreased the elevated hepatic lipids accumulation and attenuated liver fibrosis by reducing hepatic collagen deposition in mice fed with MCD diet. CGA abrogated the activation of hepatic stellate cells (HSCs) and promoted mitochondrial biogenesis both in vivo and in vitro. Moreover, the CGA-provided inhibition on HSCs activation in vitro was obviously disappeared after the application of peroxisome proliferator-activated receptor gamma, coactivator 1alpha (PGC1α) siRNA. CGA reduced the enhanced hepatic extracellular matrix (ECM) expression and the elevated serum high-mobility group box 1 (HMGB1) content in mice fed with MCD diet. CGA decreased the HMGB1-induced ECM production in both human liver sinusoidal endothelial cells and human umbilical vein endothelial cells. CGA also weakly promoted mitochondrial biogenesis in both liver sinusoidal endothelial cells and human umbilical vein endothelial cells incubated with HMGB1. Hence, CGA ameliorated hepatic fibrosis in mice fed with MCD diet through inhibiting HSCs activation via promoting mitochondrial biogenesis and reducing the HMGB1-initiated ECM production in hepatic vascular endothelial cells.
非酒精性脂肪性肝炎是最常见的慢性肝病之一，是一种进行性非酒精性脂肪性肝病，伴有肝纤维化的发展。绿原酸（CGA）是一种天然多酚化合物。本研究旨在观察 CGA 对蛋氨酸和胆碱缺乏（MCD）饮食诱导的非酒精性脂肪性肝炎小鼠肝纤维化的缓解作用，并阐明其作用机制。CGA 通过减少 MCD 饮食喂养小鼠肝脏胶原沉积，减轻肝细胞损伤，降低升高的肝脂质积累，减轻肝纤维化。CGA 在体内和体外均阻断肝星状细胞（HSCs）的激活并促进线粒体生物发生。此外，在用过氧化物酶体增殖物激活受体γ共激活剂 1α（PGC1α）siRNA 处理后，CGA 在体外对 HSCs 激活的抑制作用明显消失。CGA 降低了 MCD 饮食喂养小鼠增强的肝细胞外基质（ECM）表达和升高的血清高迁移率族蛋白 1（HMGB1）含量。CGA 降低了 HMGB1 诱导的人肝窦内皮细胞和人脐静脉内皮细胞中 ECM 的产生。CGA 还在孵育 HMGB1 的肝窦内皮细胞和人脐静脉内皮细胞中弱促进线粒体生物发生。因此，CGA 通过促进线粒体生物发生和减少肝血管内皮细胞中 HMGB1 引发的 ECM 产生，改善 MCD 饮食喂养小鼠的肝纤维化。
