Jung Nyeo Chun1, Sang-Yeob Kim2, Eun-Jung Park3, Eun Jung Kwon3, Dong-Jun Bae4, In-San Kim4, Hye Kyung Kim5, Jong Kwan Park5, Sung Won Lee6, Hyun Ho Park7, Insuk So1, Ju-Hong Jeon8. 1. Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul 110-799, Republic of Korea. 2. Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea; Department of Medicine, University of Ulsan, College of Medicine, Seoul 138-736, Republic of Korea. 3. Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. 4. Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea. 5. Department of Urology, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju 561-712, Republic of Korea. 6. Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea. 7. Department of Biotechnology, Yeungnam University, Gyeongsan 712-749, Republic of Korea. 8. Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address: jhjeon2@snu.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis fruit extract (SCE) has been used as a traditional oriental medicine for treating vascular diseases. However, the pharmacologic effects and mechanisms of SCE on vascular fibrosis are still largely unknown. Transforming growth factor β1 (TGFβ1)-mediated cellular changes are closely associated with the pathogenesis of vascular fibrotic diseases. Particularly, TGFβ1 induces actin stress fiber formation that is a crucial mechanism underlying vascular smooth muscle cell (VSMC) migration in response to vascular injury. In this study, we investigated the effect of SCE and its active ingredients on TGFβ1-induced stress fiber assembly in A7r5 VSMCs. MATERIALS AND METHODS: To investigate pharmacological actions of SCE and its ingredients on TGFβ1-treated VSMCs, we have employed molecular and cell biological technologies, such as confocal microscopy, fluorescence resonance energy transfer, western blotting, and radiometric enzyme analyses. RESULTS: We found that SCE inhibited TGFβ1-induced stress fiber formation and cell migration. Schisandrin B (SchB) showed the most prominent effect among the active ingredients of SCE tested. SchB reduced TGFβ1-mediated phosphorylation of myosin light chain, and this effect was independent of RhoA/Rho-associated kinase pathway. Fluorescence resonance energy transfer and radiometric enzyme assays confirmed that SchB inhibited myosin light chain kinase activity. We also showed that SchB decreased TGFβ1-mediated induction of α-smooth muscle actin by inhibiting Smad signaling. CONCLUSIONS: The present study demonstrates that SCE and its active ingredient SchB suppressed TGFβ1-induced stress fiber formation at the molecular level. Therefore, our findings may help future investigations to develop multi-targeted therapeutic strategies that attenuate VSMC migration and vascular fibrosis.
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis fruit extract (SCE) has been used as a traditional oriental medicine for treating vascular diseases. However, the pharmacologic effects and mechanisms of SCE on vascular fibrosis are still largely unknown. Transforming growth factor β1 (TGFβ1)-mediated cellular changes are closely associated with the pathogenesis of vascular fibrotic diseases. Particularly, TGFβ1 induces actin stress fiber formation that is a crucial mechanism underlying vascular smooth muscle cell (VSMC) migration in response to vascular injury. In this study, we investigated the effect of SCE and its active ingredients on TGFβ1-induced stress fiber assembly in A7r5 VSMCs. MATERIALS AND METHODS: To investigate pharmacological actions of SCE and its ingredients on TGFβ1-treated VSMCs, we have employed molecular and cell biological technologies, such as confocal microscopy, fluorescence resonance energy transfer, western blotting, and radiometric enzyme analyses. RESULTS: We found that SCE inhibited TGFβ1-induced stress fiber formation and cell migration. Schisandrin B (SchB) showed the most prominent effect among the active ingredients of SCE tested. SchB reduced TGFβ1-mediated phosphorylation of myosin light chain, and this effect was independent of RhoA/Rho-associated kinase pathway. Fluorescence resonance energy transfer and radiometric enzyme assays confirmed that SchB inhibited myosin light chain kinase activity. We also showed that SchB decreased TGFβ1-mediated induction of α-smooth muscle actin by inhibiting Smad signaling. CONCLUSIONS: The present study demonstrates that SCE and its active ingredient SchB suppressed TGFβ1-induced stress fiber formation at the molecular level. Therefore, our findings may help future investigations to develop multi-targeted therapeutic strategies that attenuate VSMC migration and vascular fibrosis.
Authors: Hoon Jang; Woong Jin Bae; Su Jin Kim; Hyuk Jin Cho; Seung Mo Yuk; Dong Seok Han; Chang Shik Youn; Eun Bi Kwon; Sung Yeoun Hwang; Sae Woong Kim Journal: BMC Complement Altern Med Date: 2017-02-24 Impact factor: 3.659
Authors: Soonbum Park; Eun A Cho; Jung Nyeo Chun; Da Young Lee; Sanghoon Lee; Mi Yeon Kim; Sang Mun Bae; Su In Jo; So Hee Lee; Hyun Ho Park; Tae Min Kim; Insuk So; Sang-Yeob Kim; Ju-Hong Jeon Journal: Exp Mol Med Date: 2022-08-23 Impact factor: 12.153