Oxyresveratrol (OXY) is a naturally occurring polyhydroxylated stilbene that is abundant in mulberry wood (Morus alba L.), which has frequently been supplied as a herbal medicine. It has been shown that OXY has regulatory effects on inflammation and oxidative stress, and may have potential in preventing or curing nonalcoholic fatty liver disease (NAFLD). This study examined the effects of OXY on in vitro model of NAFLD in hepatocyte by the liver X receptor α (LXRα)-mediated induction of lipogenic genes and in vivo model in mice along with its molecular mechanism. OXY inhibited the LXRα agonists-mediated sterol regulatory element binding protein-1c (SREBP-1c) induction and expression of the lipogenic genes and upregulated the mRNA of fatty acid β-oxidation-related genes in hepatocytes, which is more potent than genistein and daidzein. OXY also induced AMP-activated protein kinase (AMPK) activation in a time-dependent manner. Moreover, AMPK activation by the OXY treatment helped inhibit SREBP-1c using compound C as an AMPK antagonist. Oral administration of OXY decreased the Oil Red O stained-positive areas significantly, indicating lipid droplets and hepatic steatosis regions, as well as the serum parameters, such as fasting glucose, total cholesterol, and low density lipoprotein-cholesterol in high fat diet fed-mice, as similar with orally treatment of atorvastatin. Overall, this result suggests that OXY has the potency to inhibit hepatic lipogenesis through the AMPK/SREBP-1c pathway and can be used in the development of pharmaceuticals to prevent a fatty liver.

土白藜芦醇（OXY）是一种天然存在的多羟基二苯乙烯，在桑树（Morus alba L.）中含量丰富，桑树木经常作为草药提供。已经表明，OXY对炎症和氧化应激具有调节作用，并且可能具有预防或治疗非酒精性脂肪肝疾病（NAFLD）的潜力。本研究通过肝X受体α（LXRα）介导的脂肪形成基因诱导和体内研究OXY对肝细胞NAFLD体外模型的影响小鼠模型及其分子机制。OXY抑制LXRα激动剂介导的固醇调节元件结合蛋白1c（SREBP-1c）的诱导和生脂基因的表达，并上调肝细胞中与脂肪酸β-氧化相关的基因的mRNA，这比金雀异黄素和大豆苷元更有效。OXY还以时间依赖性方式诱导AMP激活的蛋白激酶（AMPK）激活。此外，通过使用化合物C作为AMPK拮抗剂，通过OXY处理激活AMPK有助于抑制SREBP-1c。口服OXY可显着降低油红O染色阳性区域，表明高脂饮食喂养的血脂和肝脂肪变性区域以及血清参数，如空腹血糖，总胆固醇和低密度脂蛋白胆固醇，老鼠，与口服阿托伐他汀相似。总体而言，该结果表明OXY具有通过AMPK / SREBP-1c途径抑制肝脂肪生成的潜能，可用于药物开发，以预防脂肪肝。