Dihydromyricetin alleviates endothelial inflammatory response through IRE1α/NF-κB signaling pathway in sepsis

Abstract

IntroductionThe high mortality of sepsis is closely related to disorder of coagulation induced by endothelial inflammatory response. Our aim is to investigate the protective effects of Dihydromyricetin (DHM) on endothelial cells in sepsis and the endoplasmic reticulum (ER) stress mechanism.Material and methodsIn vivo, we conducted an animal study for which fifty male Wistar rats were randomly and equally divided into five groups: sham group, cecal ligation and puncture (CLP) group and three CLP+ DHM (50, 100, 150 mg/kg) groups, the DHM was orally administered 2 h after CLP for 3 days (once per day). In vitro, human umbilical vein endothelial cells (HUVECs) were treated with DHM (50μmol) for 24 h after stimulation by lipopolysaccharide (LPS). In the inhibition groups, reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC, 3 mmol) and endoplasmic reticulum (ER) stress inhibitor (STF-083010, 10 μmol) were incubated prior to LPS.ResultsOur results indicated that DHM (150 mg/kg) alleviated the histopathological injury of endothelium, decreased the release of inflammatory cytokines and adhesion molecules such as interleukin-1β (IL-1β), interleukin-6 (IL-6) , tumor necrosis factor alpha (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET-1), and inhibited the production of ROS production. In addition, we found that DHM ameliorated ER damage, significantly decreased the protein expressions of IRE1α/NF-κB signaling pathway.ConclusionsDHM treatment alleviated inflammatory response of endothelial cells in sepsis through the IRE1α/NF-κB signaling pathway triggered by oxidative stress. This study provided experimental rationale for the treatment of DHM on therapy of sepsis.