Lu Xi, Yuan Zhi-Yi, Yan Xiao-Jin, Lei Fan, Jiang Jing-Fei, Yu Xuan, Yang Xiu-Wei, Xing Dong-Ming, DU Li-Jun
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
Chin J Nat Med. 2016 Sep;14(9):641-652. doi: 10.1016/S1875-5364(16)30076-0.
Angelica dahurica (A. dahurica) is a traditional Chinese medicinal plant being used in clinical practice. The present study demonstrated that A. dahurica could reduce white-fat weight in high-fat-diet hyperlipidemic mice, decrease total cholesterol and triglyceride concentrations in the livers of both high-fat-diet and Triton WR1339 induced hyperlipidemic mice, and enhance the total hepatic lipase activities of them. These findings were further supported by the results derived from the experiments with HepG2 cells in vitro. In addition, the proteins related to lipids metabolism were investigated using LC-MS/MS, indicating that genes of lipid metabolism and lipid transport were regulated by A. dhurica. The results from LC-MS/MS were further conformed by Western blot and real time PCR assays. A. dahurica could down-regulate the expression of catalase (CAT) and sterol carrier protein2 (SCP2) and up-regulate the expression of lipid metabolism related genes-lipase member C (LIPC) and peroxisome proliferator-activated receptor gamma (PPARγ). In the Triton WR1339 mouse liver and HepG2 cells in vitro, A. dahurica was able to increase the expression of LIPC and PPARγ, confirming the results from in vivo experiments. Imperatorin showed the same activity as A. dahurica, suggesting it was one of the major active ingredients of the herb. In conclusion, our work represented a first investigation demonstrating that A. dahurica was able to regulate lipid metabolism and could be developed as a novel approach to fighting against fatty liver and obesity.
白芷是一种用于临床实践的传统中药材。本研究表明,白芷可降低高脂饮食高脂血症小鼠的白色脂肪重量,降低高脂饮食和Triton WR1339诱导的高脂血症小鼠肝脏中的总胆固醇和甘油三酯浓度,并增强它们的肝脏总脂肪酶活性。体外HepG2细胞实验结果进一步支持了这些发现。此外,使用液相色谱-串联质谱法(LC-MS/MS)研究了与脂质代谢相关的蛋白质,表明脂质代谢和脂质转运基因受白芷调控。LC-MS/MS的结果通过蛋白质免疫印迹法(Western blot)和实时荧光定量聚合酶链反应(real time PCR)分析进一步得到证实。白芷可下调过氧化氢酶(CAT)和固醇载体蛋白2(SCP2)的表达,并上调脂质代谢相关基因——脂肪酶成员C(LIPC)和过氧化物酶体增殖物激活受体γ(PPARγ)的表达。在体外Triton WR1339小鼠肝脏和HepG2细胞中,白芷能够增加LIPC和PPARγ的表达,证实了体内实验的结果。欧前胡素显示出与白芷相同的活性,表明它是该草药的主要活性成分之一。总之,我们的工作首次表明白芷能够调节脂质代谢,并可开发成为对抗脂肪肝和肥胖症的新方法。