Schisandrol B and schisandrin B inhibit TGFβ1-mediated NF-κB activation via a Smad-independent mechanism
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Jung Nyeo Chun1,2,*, Soonbum Park1,*, Sanghoon Lee3, Jae-Kyung Kim1, Eun-Jung Park1, MinJi Kang1, Hye Kyung Kim4,5, Jong Kwan Park5, Insuk So1,2 and Ju-Hong Jeon1,2
1Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
2Institute of Human-Environment Interface Biology, Seoul National University, Seoul 03080, Korea
3Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA
4College of Pharmacy, Kyungsung University, Busan 48434, Korea
5Department of Urology, Medical School, and Institute for Medical Sciences, Chonbuk National University, Jeonju 54896, Korea
*These authors contributed equally to this work
Ju-Hong Jeon, email: email@example.com
Keywords: schisandra chinensis; schisandrol B; schisandrin B; TGFβ1; NF-κB
Received: June 30, 2017 Accepted: November 15, 2017 Published: December 14, 2017
Aberrant transforming growth factor β1 (TGFβ1) 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 TGFβ1-mediated phenotypes in vascular smooth muscle cells (VSMCs). However, it is still largely unknown about the pharmacologic effects of SCE on various TGFβ1 signaling components. In this study, we found that SCE attenuated TGFβ1-induced NF-κB 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 TGFβ1-mediated NF-κB activation. In addition, SolB and SchB effectively inhibited IKKα/β activation and IκBα phosphorylation in TGFβ1-treated VSMCs. The pharmacologic effects of SolB and SchB on NF-κB activation were independent of the Smad-mediated canonical pathway. Therefore, our study demonstrates that SCE and its active constituents SolB and SchB suppress TGFβ1-mediated NF-κB 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.
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