Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan in Anthriscus sylvestris known as cow parsley or wild chervil, and has been reported to have inhibitory effects against several pathological processes including cancer, inflammation and infection. Here, we report the effects of DPT in the fatty liver induced by high fat diet in vivo as well as its regulatory mechanism related with the transcription factor for lipogenic genes such as sterol regulatory element binding protein-1c (SREBP-1c) in vitro. C57BL/6 mice were fed high fat diet for 10 weeks and also orally administrated with DPT for additional 4 weeks. 5 and 10 mg/kg of DPT decreased lipid accumulation in the liver induced by high fat diet, as indicated by histological parameters such as Oil Red O staining and hematoxylin & eosin as well as the contents of hepatic triglyceride and cholesterol. In hepatocytes, DPT inhibited the liver X receptor α-mediated SREBP-1c induction and expression of the lipogenic genes, including fatty acid synthase, acetyl-CoA carboxylase and stearoyl-CoA desaturase-1. Moreover, DPT induced AMP-activated protein kinase (AMPK) activation, which has been known to inhibit the expression of SREBP-1c in hepatocyte. Also this compound restored the dysregulation of AMPK and SREBP-1c induced by high fat diet in mice. In conclusion, we demonstrated that DPT significantly inhibited fatty liver by adjusting lipid metabolism coordinated with AMPK activation and SREBP-1c inhibition.

脱氧鬼臼毒素 (DPT) 是一种天然存在于樟子松中的黄酮素，被称为牛欧芹或野生山萝卜，据报道对包括癌症、炎症和感染在内的多种病理过程具有抑制作用。在这里，我们报告了 DPT 在体内高脂饮食诱导的脂肪肝中的作用，以及其与脂肪生成基因转录因子相关的调节机制，例如甾醇调节元件结合蛋白-1c (SREBP-1c)体外. 给 C57BL/6 小鼠喂食高脂饮食 10 周，并口服给予 DPT 额外 4 周。5 和 10 mg/kg DPT 降低了由高脂肪饮食引起的肝脏中的脂质积累，如油红 O 染色和苏木精和伊红等组织学参数以及肝脏甘油三酯和胆固醇的含量所示。在肝细胞中，DPT 抑制肝脏 X 受体 α 介导的 SREBP-1c 诱导和脂肪生成基因的表达，包括脂肪酸合酶、乙酰辅酶 A 羧化酶和硬脂酰辅酶 A 去饱和酶 1。此外，DPT 诱导 AMP 活化蛋白激酶 (AMPK) 活化，已知其抑制肝细胞中 SREBP-1c 的表达。该化合物还恢复了小鼠高脂饮食诱导的 AMPK 和 SREBP-1c 的失调。综上所述，