Inhibition of TNF-α-induced adhesion molecule expression by diosgenin in mouse vascular smooth muscle cells via downregulation of the MAPK, Akt and NF-κB signaling pathways

Atherosclerosis is a chronic inflammatory disease and the expression of adhesion molecules on vascular smooth muscle cells (VSMCs) contributes to the progress of the disease. Diosgenin, a precursor of steroid hormones, has been shown to have a variety of biological activities including anti-inflammatory activity; however, its molecular mechanisms are poorly understood. This study examined the effect of diosgenin on the expression of adhesion molecules induced by TNF-alpha in cultured mouse VSMC cell line, MOVAS-1. Preincubation of VSMCs for 2 h with diosgenin (0.1-10 mu M) dose-dependently inhibited TNF-alpha-induced adhesion of THP-1 monocytic cells and mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Diosgenin abrogated TNF-alpha induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Diosgenin was also shown to inhibit NK-kappa B activation induced by TNF-alpha. Furthermore, diosgenin inhibited TNF-alpha-induced I kappa B kinase activation, subsequent degradation of I kappa B alpha, and nuclear translocation of NF-kappa B. Our results indicate that diosgenin inhibits the adhesive capacity of VSMC and the TNF-alpha-mediated induction of ICAM-1 and VCAM-1 in VSMC by inhibiting the MAPK/Akt/NF-kappa B signaling pathway and ROS production, which may explain the ability of diosgenin to suppress inflammation within the atherosclerotic lesion and modulate immune response. (C) 2010 Published by Elsevier Inc.