PMID- 30763696 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20190415 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 235 DP - 2019 May 10 TI - Anti-proliferative and anti-migratory effects of Scutellaria strigillosa Hemsley extracts against vascular smooth muscle cells. PG - 155-163 LID - S0378-8741(18)34247-8 [pii] LID - 10.1016/j.jep.2019.02.016 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: The abnormal increase in vascular smooth muscle cell (VSMC) proliferation and migration are critical events in the pathogenesis of cardiovascular diseases (CVDs) including restenosis and atherosclerosis. The dried roots of Scutellaria baicalensis Georgi (common name: Huangqin in China) have been confirmed to possess beneficial effects on CVD by clinical and modern pharmacological studies. Flavonoids in Huangqin exert anti-proliferative and anti-migratory effects. Similar to Huangqin, Scutellaria strigillosa Hemsley (SSH) has been used to clear heat and damp and is especially rich in flavonoids including wogonin, wogonoside, baicalein, and baicalin. However, there have been few of reports about pharmacological activities of SSH. AIM OF THE STUDY: To investigate the anti-proliferative and anti-migratory properties of Scutellaria strigillosa Hemsley extract (SSHE) in vitro and in vivo and explore its possible mechanism of action. MATERIALS AND METHODS: The chemical constituents of SSHE were analyzed by ultra-high performance liquid chromatography coupled with triple time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS). Cell proliferation and migration were investigated using BrdU incorporation assay and cell scratch test, respectively. The protein expression was determined by western blotting. In vivo, we established an artery ligation model of C57BL/6 mice and orally administered them with 50 or 100 mg/kg/day of SSHE. The carotid arteries were harvested and the intima-media thickness was examined 28 days post-ligation. RESULTS: Twelve compounds were identified and tentatively characterized. SSHE significantly inhibited the VSMC proliferation and migration stimulated by PDGF-BB and decreased the relative protein expression of regulatory signaling intermediates. Furthermore, the expression of SM22alpha was significantly elevated in SSHE-pretreated VSMCs, whereas knockdown of SM22alpha impaired the PDGF-BB-induced proliferation and migration arrest. Meanwhile, both ROS generation and the phosphorylation of ERK decreased in SSHE-pretreated VSMCs. In carotid artery ligation mice model, SSHE treatment significantly inhibited neointimal hyperplasia. CONCLUSIONS: SSHE significantly inhibited the PDGF-BB-induced VSMC proliferation, migration, and neointimal hyperplasia of carotid artery caused by ligation. Upregulation of SM22alpha expression, inhibition of ROS generation and ERK phosphorylation were, at least, partly responsible for the effects of SSHE on VSMCs. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Li, Jiankun AU - Li J AD - The Forth Affiliated Hospital of Hebei Medical University, No. 12 Health Road, Shijiazhuang 050011, PR China. Electronic address: lijiankunvp@163.com. FAU - Wang, Hairong AU - Wang H AD - Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: wel_lw@163.com. FAU - Shi, Xiaowei AU - Shi X AD - Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 11277038@qq.com. FAU - Zhao, Lili AU - Zhao L AD - Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: lilizhao2008@126.com. FAU - Lv, Tao AU - Lv T AD - Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 578405341@qq.com. FAU - Yuan, Qi AU - Yuan Q AD - Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 1434214904@qq.com. FAU - Hao, Wenyang AU - Hao W AD - Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 948931336@qq.com. FAU - Zhu, Jing AU - Zhu J AD - Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 597654544@qq.com. LA - eng PT - Journal Article DEP - 20190211 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Plant Extracts) RN - 1B56C968OA (Becaplermin) SB - IM MH - Animals MH - Becaplermin/administration & dosage MH - Carotid Intima-Media Thickness MH - Cell Movement/drug effects MH - Cell Proliferation/*drug effects MH - Chromatography, High Pressure Liquid MH - Dose-Response Relationship, Drug MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Muscle, Smooth, Vascular/cytology/*drug effects/metabolism MH - Myocytes, Smooth Muscle/drug effects/metabolism MH - Plant Extracts/administration & dosage/*pharmacology MH - Rats MH - Scutellaria/*chemistry MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Anti-migration OT - Anti-proliferative OT - Neointima hyperplasia OT - Scutellaria strigillosa Hemsley OT - VSMCs EDAT- 2019/02/15 06:00 MHDA- 2019/04/16 06:00 CRDT- 2019/02/15 06:00 PHST- 2018/11/15 00:00 [received] PHST- 2019/01/30 00:00 [revised] PHST- 2019/02/09 00:00 [accepted] PHST- 2019/02/15 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2019/02/15 06:00 [entrez] AID - S0378-8741(18)34247-8 [pii] AID - 10.1016/j.jep.2019.02.016 [doi] PST - ppublish SO - J Ethnopharmacol. 2019 May 10;235:155-163. doi: 10.1016/j.jep.2019.02.016. Epub 2019 Feb 11.