Identification of Inhibitory effects of Gomisin N from Omija (Schisandra chinensis) on Early Stage of Atherosclerosis

Abstract

Omija (Schisandra chinensis) has long been used as a food material for its unique color and taste, and also as herbal medicine for its abundant bioactive substances. Omija is known to have the protective effect against cardiovascular diseases, but its bioactive compounds and underlying mechanisms remain unclear. In this study, I compared the preventive effect of the dibenzocyclooctadiene lignans which are specific compounds in Omija on early atherosclerosis. Among the lignans rich in Omija, gomisin N most effectively attenuated adhesion of THP-1 monocytes to Human umbilical vein endothelial cells (HUVECs). Western blot, ELISA and RT-qPCR results showed that gomisin N suppressed tumor necrosis factor-alpha (TNF-α)-induced expression of vascular adhesion molecule (VCAM)-1 and monocyte chemoattractant protein (MCP)-1 related to monocyte adhesion. In addition, gomisin N downregulated the phosphorylation of proteins involved in Nuclear Factor-Kappa B (NF-κB) pathway in a concentration-dependent manner. Using a kinase profiling and IC50 assays, we elucidated that gomisin N significantly inhibited the activity of mammalian sterile-20 3 (MST3/STK24). Gomisin N also suppressed TNF-α-induced phosphorylation of ezrin/radixin/moesin (ERM), the substrate of MST3/STK24, in HUVECs. Taken together, gomisin N markedly inhibited THP-1 monocyte adherence to vascular endothelial cells by targeting MST3/STK24. Our findings suggest that gomisin N is a potential functional material for preventing early atherosclerosis.