Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
Phytother Res. 2019 Dec;33(12):3140-3152. doi: 10.1002/ptr.6486. Epub 2019 Aug 26.
Multiphase pathological processes involve in Type 2 diabetes (T2DM)-induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM-induced NAFLD were investigated. T2DM-induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM-induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM-induced production of interleukin 1 beta, interleukin 6, and TNF-α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM-induced NAFLD. In high D-glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM-induced NAFLD.
多相病理过程涉及 2 型糖尿病（T2DM）诱导的非酒精性脂肪性肝病（NAFLD）。然而，治疗方法相当有限。本研究探讨了槲皮素在 T2DM 诱导的 NAFLD 中的保肝作用及其机制。在体内和体外建立了 T2DM 诱导的 NAFLD 和槲皮素治疗模型。结果表明，槲皮素减轻了血清转氨酶水平，并显著降低了 T2DM 诱导的肝脏组织学改变。此外，槲皮素恢复了肝脏中超氧化物歧化酶、过氧化氢酶和谷胱甘肽的含量。不仅如此，槲皮素还显著减弱了 T2DM 诱导的白细胞介素 1β、白细胞介素 6 和肿瘤坏死因子-α的产生。伴随着血清总胆汁酸的增加（p=0.0001）和肝脏总胆汁酸的减少（p=0.0005）的恢复，槲皮素可以减少 db/db 小鼠肝脏中的脂质积累。进一步的机制研究表明，法尼醇 X 受体 1/Takeda G 蛋白偶联受体 5 信号通路参与了槲皮素对 T2DM 诱导的 NAFLD 中脂质代谢的调节。在高葡萄糖和游离脂肪酸共培养 HepG2 细胞模型中，槲皮素消除了脂质滴，并恢复了上调的总胆固醇和三酰甘油水平。与在小鼠中的发现相似，槲皮素也可以激活法尼醇 X 受体 1/Takeda G 蛋白偶联受体 5 信号通路。这些发现表明，槲皮素可能是治疗 T2DM 诱导的 NAFLD 的一种潜在有效药物。
