Schisandrin B suppresses TGF beta 1 signaling by inhibiting Smad2/3 and MAPK pathways

Abstract

TGF beta 1 plays a crucial role in the pathogenesis of vascular fibrotic diseases. Schisandra chinensis (S. chinensis), which is used as an oriental herbal medicine, is effective in the treatment of vascular injuries that cause aberrant TGF beta 1 signaling. In this study, we investigated whether S. chinensis extract and its active ingredients inhibit TGF beta 1 signaling in A7r5 vascular smooth muscle cells. We found that S. chinensis extract suppressed TGF beta 1 signaling via inhibition of Smad2/3 phosphorylation and nuclear translocation. Among the active ingredients of S. chinensis extract, schisandrin B (SchB) most potently inhibited TGF beta 1 signaling. SchB inhibited sustained phosphorylation and nuclear translocation of Smad2/3. Moreover, SchB suppressed TGF beta 1-induced phosphorylation of p38 and INK, which contributed to Smad2/3 inactivation. The present study is the first to demonstrate that S. chinensis extract and SchB inhibit TGF beta 1 signaling. Our results may help future investigations to understand vascular fibrosis pathogenesis and to develop novel therapeutic strategies for treatment of vascular fibrotic diseases. (C) 2011 Elsevier Inc. All rights reserved.