Schisandrol B and schisandrin B inhibit TGF?1-mediated NF-?B activation via a Smad-independent mechanism.

ABSTRACT: Aberrant transforming growth factor ?1 (TGF?1) signaling plays a pathogenic role in the development of vascular fibrosis. We have reported that Schisandra chinensis fruit extract (SCE), which has been used as a traditional oriental medicine, suppresses TGF?1-mediated phenotypes in vascular smooth muscle cells (VSMCs). However, it is still largely unknown about the pharmacologic effects of SCE on various TGF?1 signaling components. In this study, we found that SCE attenuated TGF?1-induced NF-?B activation and nuclear translocation in VSMCs. Among the five active ingredients of SCE that were examined, schisandrol B (SolB) and schisandrin B (SchB) most potently suppressed TGF?1-mediated NF-?B activation. In addition, SolB and SchB effectively inhibited IKK?/? activation and I?B? phosphorylation in TGF?1-treated VSMCs. The pharmacologic effects of SolB and SchB on NF-?B activation were independent of the Smad-mediated canonical pathway. Therefore, our study demonstrates that SCE and its active constituents SolB and SchB suppress TGF?1-mediated NF-?B signaling pathway in a Smad-independent mechanism. Our results may help further investigations to develop novel multi-targeted therapeutic strategies that treat or prevent vascular fibrotic diseases.

SUBMITTER: Chun JN 

PROVIDER: S-EPMC5790451 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature