Xi Yiyuan, Zheng Jujia, Xie Wei, Xu Xiangwei, Cho Namki, Zhou Xudong, Yu Xiaomin
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju, Korea.
Front Pharmacol. 2021 Nov 19;12:750147. doi: 10.3389/fphar.2021.750147. eCollection 2021.
An overload of hepatic fatty acids, such as oleic acid is a key trigger of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether , a valuable traditional medicine used to treat various diseases, could mitigate OA-induced lipid accumulation in HepG2 cells. Then, to identify the active substances in , a phytochemistry investigation was conducted using a bioassay-guided isolation method. Consequently, one terpene () and one flavone () were identified. Compound ((+)-dehydrovomifoliol) exhibited potent effects against lipid accumulation in OA-induced HepG2 cells, without causing cyto-toxicity. Notably, treatment with (+)-dehydrovomifoliol decreased the expression levels of three genes related to lipogenesis ( and ) and increased those of three genes related to fatty acid oxidation ( and ). In addition, similar results were observed for SREBP1, PPARα, and FGF21 protein levels. The effects of (+)-dehydrovomifoliol were partially reversed by treatment with the PPARα antagonist GW6471, indicating the important role of the PPARα-FGF21 axis in the effects of (+)-dehydrovomifoliol. Based on its effects on hepatic lipogenesis and fatty acid oxidation signaling via the PPARα-FGF21 axis, (+)-dehydrovomifoliol isolated from could be a useful early lead compound for developing new drugs for NAFLD prevention.
肝脏脂肪酸过载，如油酸，是非酒精性脂肪性肝病（NAFLD）的关键触发因素。在此，我们研究了一种用于治疗多种疾病的珍贵传统药物是否可以减轻油酸诱导的HepG2细胞中的脂质积累。然后，为了鉴定该传统药物中的活性物质，采用生物测定导向分离法进行了植物化学研究。结果，鉴定出一种萜类化合物（）和一种黄酮类化合物（）。化合物（（+）-脱氢催吐萝芙木醇）对油酸诱导的HepG2细胞中的脂质积累具有显著作用，且不引起细胞毒性。值得注意的是，用（+）-脱氢催吐萝芙木醇处理可降低与脂肪生成相关的三个基因（和）的表达水平，并增加与脂肪酸氧化相关的三个基因（和）的表达水平。此外，在SREBP1、PPARα和FGF21蛋白水平上也观察到了类似的结果。用PPARα拮抗剂GW6471处理可部分逆转（+）-脱氢催吐萝芙木醇的作用，表明PPARα-FGF21轴在（+）-脱氢催吐萝芙木醇的作用中起重要作用。基于其通过PPARα-FGF21轴对肝脏脂肪生成和脂肪酸氧化信号传导的影响，从该传统药物中分离出的（+）-脱氢催吐萝芙木醇可能是开发预防NAFLD新药的有用早期先导化合物。
