Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China.
Department of Pharmacy, Maternal and Child Health Care Hospital of Zigong, Zigong, Sichuan, China.
J Gastroenterol Hepatol. 2018 Feb;33(2):533-542. doi: 10.1111/jgh.13884.
Nonalcoholic fatty liver disease (NAFLD) has become a major health concern worldwide. The present study was designed to investigate the effects of calycosin against high-fat diet (HFD)-induced NAFLD in mice.
C57BL/6 J male mice were fed with HFD to induce NAFLD model and treated with or without calycosin for 12 weeks. The levels of ALT, AST, insulin, and adiponectin were measured using biochemical methods. Hemotoxylin and eosin staining and Oil Red O staining were used to determine the liver histopathology changes and measure the degree of lipid accumulation respectively. Glucose tolerance tests and insulin tolerance tests were performed followed by quantitative insulin sensitivity check index determination. Western blot and quantitative real-time polymerase chain reaction were used to explore the potential mechanism involved in the beneficial effects of calycosin.
Calycosin effectively decreased the levels of ALT and AST, increased the levels of adiponectin and insulin. Hemotoxylin and eosin staining indicated calycosin treatment remarkably improved liver injury. Oil Red O staining indicated calycosin treatment remarkably improved lipid accumulation. Quantitative insulin sensitivity check index in HFD fed mice was significantly lower than in the standard chow fed mice. Further, calycosin suppressed phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, sterol-regulatory element binding protein 1c, and FASN involved in gluconeogenesis and triglyceride synthesis. Calycosin increased glycogen synthase kinase 3 beta, glucose transporter 4, and phosphorylated insulin receptor substrates 1 and 2 expressions involved in glucose metabolism. The aforementioned beneficial effects of calycosin against HFD-induced NAFLD may be attributed to farnesoid X receptor activation.
Calycosin could produce the favorable effects against HFD-induced NAFLD in mice.
非酒精性脂肪性肝病（NAFLD）已成为全球主要的健康关注点。本研究旨在探讨毛蕊异黄酮对高脂饮食（HFD）诱导的小鼠非酒精性脂肪性肝病的作用。
采用 C57BL/6J 雄性小鼠饲喂 HFD 诱导 NAFLD 模型，并用或不用毛蕊异黄酮治疗 12 周。采用生化方法测定 ALT、AST、胰岛素和脂联素水平。采用苏木精和伊红染色和油红 O 染色分别测定肝组织病理学变化和脂质蓄积程度。进行葡萄糖耐量试验和胰岛素耐量试验，随后测定定量胰岛素敏感指数。采用 Western blot 和实时定量聚合酶链反应探索毛蕊异黄酮有益作用的潜在机制。
毛蕊异黄酮有效降低 ALT 和 AST 水平，增加脂联素和胰岛素水平。苏木精和伊红染色表明毛蕊异黄酮治疗显著改善肝损伤。油红 O 染色表明毛蕊异黄酮治疗显著改善脂质蓄积。HFD 喂养小鼠的定量胰岛素敏感指数明显低于标准饲料喂养小鼠。此外，毛蕊异黄酮抑制参与糖异生和甘油三酯合成的磷酸烯醇丙酮酸羧激酶、葡萄糖-6-磷酸酶、固醇调节元件结合蛋白 1c 和 FASN。毛蕊异黄酮增加参与葡萄糖代谢的糖原合酶激酶 3β、葡萄糖转运蛋白 4 和磷酸化胰岛素受体底物 1 和 2 的表达。毛蕊异黄酮对 HFD 诱导的 NAFLD 的上述有益作用可能归因于法尼醇 X 受体的激活。
毛蕊异黄酮可对 HFD 诱导的小鼠非酒精性脂肪性肝病产生有利影响。
