Department of Pharmacology, Nantong University Pharmacy College, Nantong 226001, China.
Department of Pharmacology, Nantong University Pharmacy College, Nantong 226001, China.
Phytomedicine. 2019 Sep;62:152935. doi: 10.1016/j.phymed.2019.152935. Epub 2019 Apr 22.
Polydatin has been recently shown to possess extensive cardiovascular pharmacological activities. However, its protective effect against atherosclerosis in vivo remains poorly understood. The aim of the present study was to evaluate the potential effects of polydatin on high fat diet (HFD)-induced atherosclerosis using ApoE mice, and explore the underlying mechanisms involved, especially focusing on reverse cholesterol transport (RCT) regulation.
after 12 weeks treatment, serum samples, mouse aorta, liver, peritoneal macrophages were collected to determine lipid profiles, atherosclerotic lesions, hepatic steatosis, foam cell formation and expression of related molecules. RAW264.7 macrophages were used to study cholesterol efflux.
Polydatin improved serum lipid profiles, attenuated atherosclerosis and hepatic steatosis. Furthermore, polydatin may facilitate RCT by stimulating cholesterol efflux through ATP-binding cassette transporters (ABC) A1, ABCG1 and scavenger receptor class B type I (SR-BI) in macrophages, increasing serum levels of high density lipoprotein and apolipoprotein A-I, promoting of SR-BI-mediated cholesterol uptake of liver, increasing secretion of cholesterol into bile by ABCG5/ABCG8 and improving cholesterol metabolism by CYP7A1 pathway. Polydatin also regulated the protein expressions of hepatic fatty acid synthase and peroxisome proliferator-activated receptor-α. Additionally, polydatin reduced hepatic and aortic reactive oxygen species generation, normalized activities of antioxidant enzymes and increased protein expressions of NADPH-oxidase (NOX) 2 and NOX4 in liver. Polydatin also prevented hepatic and aortic inflammation as evidenced by the reduced macrophage infiltration and mRNA expressions of tumor necrosis factor-α and interleukin-6 in both aorta and liver.
These findings indicated that polydatin can inhibit atherosclerosis through enhancement of overall RCT. In addition, anti-oxidative and anti-inflammatory effect of polydatin may also contribute to its inhibitory effects on atherosclerosis.
白藜芦醇苷最近被证明具有广泛的心血管药理活性。然而，其在体内对动脉粥样硬化的保护作用仍知之甚少。本研究旨在评价白藜芦醇苷对载脂蛋白 E 基因敲除（ApoE-/-）小鼠高脂饮食诱导的动脉粥样硬化的潜在作用，并探讨其相关机制，特别是关注胆固醇逆转运（RCT）的调节。
经过 12 周的治疗后，收集血清样本、小鼠主动脉、肝脏、腹腔巨噬细胞，以测定血脂谱、动脉粥样硬化病变、肝脂肪变性、泡沫细胞形成和相关分子的表达。用 RAW264.7 巨噬细胞研究胆固醇外流。
白藜芦醇苷改善了血清脂质谱，减轻了动脉粥样硬化和肝脂肪变性。此外，白藜芦醇苷可能通过刺激 ATP 结合盒转运蛋白（ABC）A1、ABCG1 和清道夫受体 B 型 I（SR-BI）促进胆固醇外流，增加高密度脂蛋白和载脂蛋白 A-I 水平，促进肝脏中 SR-BI 介导的胆固醇摄取，增加 ABCG5/ABCG8 介导的胆固醇排入胆汁，改善 CYP7A1 通路的胆固醇代谢，从而促进 RCT。白藜芦醇苷还调节了肝脂肪酸合酶和过氧化物酶体增殖物激活受体-α的蛋白表达。此外，白藜芦醇苷降低了肝和主动脉的活性氧生成，使抗氧化酶的活性正常化，并增加了肝中 NADPH 氧化酶（NOX）2 和 NOX4 的蛋白表达。白藜芦醇苷还通过减少巨噬细胞浸润和主动脉及肝脏中肿瘤坏死因子-α和白细胞介素-6 的 mRNA 表达来预防肝和主动脉的炎症。
这些发现表明，白藜芦醇苷可以通过增强整体 RCT 来抑制动脉粥样硬化。此外，白藜芦醇苷的抗氧化和抗炎作用也可能有助于其抑制动脉粥样硬化的作用。
