Liu Qingsheng, Pan Ran, Ding Lei, Zhang Fuli, Hu Linfeng, Ding Bin, Zhu Linwensi, Xia Yongliang, Dou Xiaobing
The Guang Xing Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China.
College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China; Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, PR China.
Int Immunopharmacol. 2017 Aug;49:132-141. doi: 10.1016/j.intimp.2017.05.026. Epub 2017 Jun 1.
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Rutin is a natural flavonoid with significant roles in combating cellular oxidative stress and regulating lipid metabolism. The current study aims to investigate the molecular mechanisms underlying rutin's hypolipidemic and hepatoprotective effects in nonalcoholic fatty liver disease. Rutin treatment was applied to male C57BL/6 mice maintained on a high-fat diet and HepG2 cells challenged with oleic acid. Hepatic lipid accumulation was evaluated by triglyceride assay and Oil Red O staining. Oxidative hepatic injury was assessed by malondialdehyde assay, superoxide dismutase assay and reactive oxygen species assay. The expression levels of various lipogenic and lipolytic genes were determined by quantitative real-time polymerase chain reactions. In addition, liver autophagy was investigated by enzyme-linked immunosorbent assay. In both fat-challenged murine liver tissues and HepG2 cells, rutin treatment was shown to significantly lower triglyceride content and the abundance of lipid droplets. Rutin was also found to reduce cellular malondialdehyde level and restore superoxide dismutase activity in hepatocytes. Among the various lipid-related genes, rutin treatment was able to restore the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its downstream targets, carnitine palmitoyltransferase 1 and 2 (CPT-1 and CPT-2), while suppressing those of sterol regulatory element-binding protein 1c (SREBP-1c), diglyceride acyltransfase 1 and 2 (DGAT-1 and 2), as well as acyl-CoA carboxylase (ACC). In addition, rutin was shown to repress the autophagic function of liver tissues by down-regulating key autophagy biomarkers, including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β). The experimental data demonstrated that rutin could reduce triglyceride content and mitigate oxidative injuries in fat-enriched hepatocytes. The hypolipidemic properties of rutin could be attributed to its ability to simultaneously facilitate fatty acid metabolism and inhibit lipogenesis.
非酒精性脂肪性肝病（NAFLD）的特征是肝脏脂质过度积累和肝细胞氧化损伤。芦丁是一种天然黄酮类化合物，在对抗细胞氧化应激和调节脂质代谢方面具有重要作用。当前研究旨在探究芦丁在非酒精性脂肪性肝病中降血脂和肝脏保护作用的分子机制。将芦丁处理应用于维持高脂饮食的雄性C57BL/6小鼠以及用油酸刺激的HepG2细胞。通过甘油三酯测定和油红O染色评估肝脏脂质积累。通过丙二醛测定、超氧化物歧化酶测定和活性氧测定评估肝脏氧化损伤。通过定量实时聚合酶链反应测定各种生脂和脂解基因的表达水平。此外，通过酶联免疫吸附测定研究肝脏自噬。在脂肪攻击的小鼠肝脏组织和HepG2细胞中，芦丁处理均显示可显著降低甘油三酯含量和脂滴丰度。还发现芦丁可降低细胞丙二醛水平并恢复肝细胞中超氧化物歧化酶活性。在各种脂质相关基因中，芦丁处理能够恢复过氧化物酶体增殖物激活受体α（PPAR-α）及其下游靶点肉碱棕榈酰转移酶1和2（CPT-1和CPT-2）的表达，同时抑制固醇调节元件结合蛋白1c（SREBP-1c）、二酰甘油酰基转移酶1和2（DGAT-1和DGAT-2）以及酰基辅酶A羧化酶（ACC）的表达。此外，芦丁通过下调关键自噬生物标志物，包括肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β），显示出抑制肝脏组织自噬功能的作用。实验数据表明，芦丁可降低甘油三酯含量并减轻富含脂肪的肝细胞中的氧化损伤。芦丁的降血脂特性可归因于其同时促进脂肪酸代谢和抑制脂肪生成的能力。
