Nutrition and Obesity Group, Department of Nutrition and Food Science, Faculty of Pharmacy, University of Basque Country (UPV/EHU) and Lucio Lascaray Research Center, 01006 Vitoria-Gasteiz, Spain.
BIOARABA Institute of Health, 01009 Vitoria-Gasteiz, Spain.
Molecules. 2020 Nov 20;25(22):5444. doi: 10.3390/molecules25225444.
Pterostilbene is a dimethyl ether derivative of resveratrol, less metabolized than its analogue, due to the substitution of two hydroxyl groups with methoxyl groups. Nevertheless, the amounts of pterostilbene phase II metabolites found in plasma and tissues are higher than those of the parent compound. The first aim of this study was to assess whether pterostilbene-4'--glucuronide (PT-G) and pterostilbene-4'--sulfate (PT-S) were able to prevent triglyceride accumulation in AML12 (alpha mouse liver 12) hepatocytes. This being the case, we aimed to analyze the mechanisms involved in their effects. For this purpose, an in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10 or 25 µM of pterostilbene, pterostilbene-4'--glucuronide or pterostilbene-4'--sulfate for 18 h. Triglycerides and cell viability were assessed by a commercial kit and crystal violet assay, respectively. Protein expression of enzymes and transporters involved in triglyceride metabolism was analyzed by immunoblot. The results showed for the first time the anti-steatotic effect of pterostilbene metabolites and thus, that they contribute to the preventive effect induced by pterostilbene on steatosis in in vivo models. This anti-steatotic effect is mainly due to the inhibition of de novo lipogenesis.
紫檀芪是白藜芦醇的二甲醚衍生物，由于两个羟基被甲氧基取代，其代谢物比其类似物少。然而，在血浆和组织中发现的紫檀芪相 II 代谢物的量高于母体化合物。本研究的首要目的是评估紫檀芪-4'-葡萄糖苷（PT-G）和紫檀芪-4'-硫酸盐（PT-S）是否能够防止 AML12（α小鼠肝 12）肝细胞中甘油三酯的积累。如果是这样，我们旨在分析其作用涉及的机制。为此，通过用棕榈酸（PA）孵育鼠 AML12 肝细胞，开发了一种体外模型来模拟脂肪肝中的肝细胞情况。对于细胞处理，将肝细胞与 1、10 或 25µM 的紫檀芪、紫檀芪-4'-葡萄糖苷或紫檀芪-4'-硫酸盐孵育 18 小时。通过商业试剂盒评估甘油三酯和细胞活力，分别。通过免疫印迹分析参与甘油三酯代谢的酶和转运蛋白的蛋白表达。结果首次显示了紫檀芪代谢物的抗脂肪变性作用，因此，它们有助于紫檀芪在体内模型中对脂肪变性的预防作用。这种抗脂肪变性作用主要是由于从头合成脂质的抑制。
