2,3,4',5-Tetrahydroxystilbene-2-O-β-d-glucoside attenuates atherosclerotic progression by inhibiting inflammation via downregulation of TNF receptor-associated factor 6 expression.

Abstract

Atherosclerosis (As) is an inflammatory disease, and 2,3,4',5-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) has been shown to suppress inflammation. However, it is still unclear if TSG alleviates As by inhibiting inflammation. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess the mRNA levels of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TNF-α and interleukin-6 (IL-6) in lipoprotein E knockout (ApoE -/-) mice with As. Hematoxylin-eosin (H&E) staining was performed to examine the atherosclerotic plaques in the aortic sinus. QRT-PCR and western blotting were used to measure the expression levels of TRAF6, TNF-α, and IL-6 in human umbilical vein endothelial cells (HUVECs), and enzyme-linked immunosorbent assays (ELISAs) were performed to monitor the levels of TNF-α and IL-6 in serum and cell culture medium. TSG inhibited subendothelial plaques formation in the aortic sinus and inhibited the levels of total cholesterol (TCHO), low-density lipoprotein (LDL), TRAF6, TNF-α and IL-6 in AS mice in a dose-dependent manner. Moreover, TSG attenuated the oxidatively modified LDL (ox-LDL)-induced increases in TRAF6, TNF-α and IL-6 expression, whereas TRAF6 overexpression reversed the TSG-induced decreases in TRAF6, TNF-α, and IL-6 expression in HUVECs. TSG attenuates atherosclerotic progression by inhibiting inflammation via the downregulation of TRAF6 in ApoE-/- mice and HUVECs.