Kim Myungsuk, Yoo GyHye, Randy Ahmad, Kim Hyoung Seok, Nho Chu Won
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
Mol Nutr Food Res. 2017 May;61(5). doi: 10.1002/mnfr.201600632. Epub 2017 Feb 22.
Nonalcoholic fatty liver diseases (NAFLD) range histopathologically from hepatic steatosis to steatohepatitis. Chicoric acid has beneficial effects on obesity and liver injury, but its effects on nonalcoholic steatohepatitis (NASH) have not yet been determined. This study examined the effects of Crepidiastrum denticulatum extract (CDE) and its active compound chicoric acid in a mouse model of NASH and fibrosis.
CDE and chicoric acid were orally administrated to mice fed a methionine- and choline-deficient (MCD) diet. HepG2 and AML-12 cells in MCD medium were incubated with chicoric acid. MCD-fed mice developed the histopathological characteristics of human NASH, including altered regulation of lipid metabolism, inflammation, fibrosis, and oxidation-associated expression, along with augmented lipoperoxidation. Administration of CDE or chicoric acid to MCD-fed mice and HepG2 and AML-12 cells in MCD medium reduced oxidative stress by upregulating antioxidant enzymes and decreased inflammation by inhibiting proinflammatory cytokines and nuclear factor-κB activation. In addition, CDE or chicoric acid reduced fibrosis, apoptosis, and lipogenesis-related gene expression and increased AMP Kinase activation both in vivo and in vitro.
CDE and chicoric acid may be effective in the treatment of NAFLD and NASH.
非酒精性脂肪性肝病（NAFLD）在组织病理学上范围从肝脂肪变性到脂肪性肝炎。菊苣酸对肥胖和肝损伤具有有益作用，但其对非酒精性脂肪性肝炎（NASH）的作用尚未确定。本研究在NASH和肝纤维化小鼠模型中检测了苣荬菜提取物（CDE）及其活性化合物菊苣酸的作用。
将CDE和菊苣酸口服给予喂食蛋氨酸和胆碱缺乏（MCD）饮食的小鼠。在MCD培养基中的HepG2和AML-12细胞用菊苣酸孵育。喂食MCD的小鼠出现了人类NASH的组织病理学特征，包括脂质代谢调节改变、炎症、纤维化和氧化相关表达改变，以及脂质过氧化增加。给喂食MCD的小鼠以及MCD培养基中的HepG2和AML-12细胞施用CDE或菊苣酸，通过上调抗氧化酶降低氧化应激，并通过抑制促炎细胞因子和核因子-κB活化减少炎症。此外，CDE或菊苣酸在体内和体外均降低了纤维化、细胞凋亡和脂肪生成相关基因的表达，并增加了AMP激酶的活化。
CDE和菊苣酸可能对NAFLD和NASH的治疗有效。
