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

Eur Rev Med Pharmacol Sci. 2023 May;27(10):4369-4377. doi: 10.26355/eurrev_202305_32441.

Abstract

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusions: TSG attenuates atherosclerotic progression by inhibiting inflammation via the downregulation of TRAF6 in ApoE-/- mice and HUVECs.

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis* / metabolism
  • Down-Regulation
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Lipoproteins, LDL / metabolism
  • Mice
  • Mice, Knockout, ApoE
  • TNF Receptor-Associated Factor 6* / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
  • TNF Receptor-Associated Factor 6
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Lipoproteins, LDL
  • Apolipoproteins E