Lin Pei, Lu Jian-Mei, Wang Yan-Fang, Gu Wen, Zhao Rong-Hua, Yu Jie
Department of Pharmacy, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China.
Department of Oriental Medicinal Material and Processing, College of Life Science, Kyung Hee University, Yongin, South Korea.
Pharmacogn Mag. 2017 Apr-Jun;13(50):245-253. doi: 10.4103/0973-1296.204563. Epub 2017 Apr 18.
2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG), a natural stilbene, shows great activities in hepatic lipid regulation, especially for hepatic triglyceride lowering. However, information about its mechanisms on biosynthesis and degradation of triglyceride is still limited. This research pays close attention to clarify the mechanism of TSG on prevention of hepatic lipid accumulation.
TSG was given to steatosis hepatocyte L-02 cell induced by fat emulsion incubation. The contents of free fatty acid, triglyceride, rate-controlling enzymes, and transcriptional regulatory factors, which play key role in biosynthesis and decomposition of triglyceride, were determined with or without TSG exposure.
TSG could reduce the free fatty acid material supply for the synthesis of endogenous triglyceride and it did so by reducing the expression of liver type fatty acid binding protein and fatty acid transport protein 4. TS Ginhibited the expression of sterol regulatory element-binding protein 1c, and then reduce the contents of acetyl-CoA carboxylase 1 and fatty acid synthase. Therefore, TSG prevented biosynthesis of triglyceride. Mean while, TSG also promoted the decomposition of triglyceride by the activation of peroxisome proliferators activator receptors alpha.
TSG could effective intervene the accumulation of triglyceride in hepatic cell. Thus, TSG could be considered as a promising drug candidate in prevention and treatment of lipid metabolic disorders, especially nonalcoholic fatty liver disease. ACACA: Acetyl-CoA carboxylase 1, Apo-B100: Apo lipoprotein B100, FASN: Fatty acid synthase, FATP4: Fatty acid transport protein 4, FBS: Fetal bovine serum; FEN: Fenofibrate, FFA: Free fatty acid, L-FABP: Liver type fatty acid binding protein, LPL: Lipoprotein lipase, MTTP: Microsomal triglyceride transfer protein, NAFLD: Non-alcoholic fatty liver disease, PBS: Phosphate buffer saline, PPAR-α: Peroxisome proliferators activator receptors alpha, RPMI: Roswell Park Memorial Institute, SIM: Simvastatin, SREBF1c: Sterol regulatory element-binding protein 1c, TG: Triglyceride, TSG: 2, 3, 5, 4-tetrahydroxy-stilbene-2-O-β-Dglucoside, VLDL: Very low density lipoprotein.
2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷(TSG)是一种天然二苯乙烯,在肝脏脂质调节方面表现出强大活性,尤其在降低肝脏甘油三酯方面。然而,关于其在甘油三酯生物合成和降解机制方面的信息仍然有限。本研究密切关注以阐明TSG预防肝脏脂质积累的机制。
将TSG给予经脂肪乳剂孵育诱导的脂肪变性肝细胞L-02细胞。测定在有或无TSG暴露情况下,游离脂肪酸、甘油三酯、在甘油三酯生物合成和分解中起关键作用的限速酶以及转录调节因子的含量。
TSG可减少内源性甘油三酯合成的游离脂肪酸物质供应,其通过降低肝型脂肪酸结合蛋白和脂肪酸转运蛋白4的表达来实现。TSG抑制固醇调节元件结合蛋白1c的表达,进而降低乙酰辅酶A羧化酶1和脂肪酸合酶的含量。因此,TSG阻止了甘油三酯的生物合成。同时,TSG还通过激活过氧化物酶体增殖物激活受体α促进甘油三酯的分解。
TSG可有效干预肝细胞中甘油三酯的积累。因此,TSG可被视为预防和治疗脂质代谢紊乱,尤其是非酒精性脂肪性肝病的有前景的候选药物。ACACA:乙酰辅酶A羧化酶1,Apo-B100:载脂蛋白B100,FASN:脂肪酸合酶,FATP4:脂肪酸转运蛋白4,FBS:胎牛血清;FEN:非诺贝特,FFA:游离脂肪酸,L-FABP:肝型脂肪酸结合蛋白,LPL:脂蛋白脂肪酶,MTTP:微粒体甘油三酯转运蛋白,NAFLD:非酒精性脂肪性肝病,PBS:磷酸盐缓冲盐水,PPAR-α:过氧化物酶体增殖物激活受体α,RPMI:罗斯威尔帕克纪念研究所,SIM:辛伐他汀,SREBF1c:固醇调节元件结合蛋白1c,TG:甘油三酯,TSG:2,3,5,4-四羟基二苯乙烯-2-O-β-D-葡萄糖苷,VLDL:极低密度脂蛋白。