Repurposing matrine for the treatment of hepatosteatosis and associated disorders in glucose homeostasis in mice  

作　　者：Ali Mahzari Xiao-Yi Zeng Xiu Zhou Songpei Li Jun Xu Wen Tan Ross Vlahos Stephen Robinson Ji-Ming YE 

机构地区：[1]School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia [2]School of Chemical Engineering, Wuyi University, Jiangmen, China [3]Institute of Biomedicat & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China

出　　处：《Acta Pharmacologica Sinica》2018年第11期1753-1759,共7页中国药理学报（英文版）

摘　　要：The present study investigated the efficacy of the hepatoprotective drug matrine （Mtr） for its new application for hepatosteatosis and associated disorders in glucose homeostasis. The study was performed in two nutritional models of hepatosteatosis in mice with various abnormal glucose homeostasis： （1） high-fructose diet （HFru） induced hepatosteatosis and glucose intolerance from hepatic, and （2） hepatosteatosis and hyperglycemia induced by high-fat （HF） diet in combination with low doses of streptozotocin （STZ）. Administration of Mtr （100 mg/kg every day in diet for 4 weeks） abolished HFru-induced hepatosteatosis and glucose intolerance. These effects were associated with the inhibition of HFru-stimulated de novo lipogenesis （DNL） without altering hepatic fatty acid oxidation. Further investigation revealed that HFru-induced endoplasmic reticulum （ER） stress was inhibited, whereas heat-shock protein 72 （an inducible chaperon protein） was increased by Mtr. In a type 2 diabetic model induced by HF-STZ, Mtr reduced hepatosteatosis and improved attenuated hyperglycemia. The hepatoprotective drug Mtr may be repurposed for the treatment of hepatosteatosis and associated disorders in glucose homeostasis. The inhibition of ER stress associated DNL and fatty acid influx appears to play an important role in these metabolic effects.The present study investigated the efficacy of the hepatoprotective drug matrine （Mtr） for its new application for hepatosteatosis and associated disorders in glucose homeostasis. The study was performed in two nutritional models of hepatosteatosis in mice with various abnormal glucose homeostasis： （1） high-fructose diet （HFru） induced hepatosteatosis and glucose intolerance from hepatic, and （2） hepatosteatosis and hyperglycemia induced by high-fat （HF） diet in combination with low doses of streptozotocin （STZ）. Administration of Mtr （100 mg/kg every day in diet for 4 weeks） abolished HFru-induced hepatosteatosis and glucose intolerance. These effects were associated with the inhibition of HFru-stimulated de novo lipogenesis （DNL） without altering hepatic fatty acid oxidation. Further investigation revealed that HFru-induced endoplasmic reticulum （ER） stress was inhibited, whereas heat-shock protein 72 （an inducible chaperon protein） was increased by Mtr. In a type 2 diabetic model induced by HF-STZ, Mtr reduced hepatosteatosis and improved attenuated hyperglycemia. The hepatoprotective drug Mtr may be repurposed for the treatment of hepatosteatosis and associated disorders in glucose homeostasis. The inhibition of ER stress associated DNL and fatty acid influx appears to play an important role in these metabolic effects.

关 键 词：MATRINE HEPATOSTEATOSIS glucose intolerance hyperglycemic control 

分 类 号：TS245.4[轻工技术与工程—制糖工程] Q959.837[轻工技术与工程—食品科学与工程]