Introduction:
The high mortality of sepsis is closely related to a disorder of coagulation induced by the 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 methods:
In vivo, we conducted an animal study in which fifty male Wistar rats were randomly and equally divided into five groups: a sham group, a cecal ligation and puncture (CLP) group and three CLP + DHM (50, 100, 150 mg/kg) groups. The DHM was orally administered 2 hours after CLP for 3 days (once per day). In vitro, human umbilical vein endothelial cells (HUVECs) were treated with DHM (50 µmol) for 24 hours after stimulation by lipopolysaccharide (LPS). In the inhibition groups, the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC, 3 mmol) and ER stress inhibitor (STF-083010, 10 µmol) were incubated prior to LPS.

Results:
Our results indicated that DHM (150 mg/kg) alleviated the histopathological injury of the endothelium, decreased the release of inflammatory cytokines and adhesion molecules such as interleukin-1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET-1), and inhibited the production of ROS. In addition, we found that DHM ameliorated ER damage, and significantly decreased the protein expression of the IRE1α/NF-κB signaling pathway.

Conclusions:
Dihydromyricetin treatment alleviated the inflammatory response of endothelial cells in sepsis through the IRE1α/NF-κB signaling pathway triggered by oxidative stress. This study provided an experimental rationale for the treatment of DHM in therapy of sepsis.