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Anti-proliferative and anti-migratory effects of Scutellaria strigillosa Hemsley extracts against vascular smooth muscle cells.

Abstract

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 SM22α was significantly elevated in SSHE-pretreated VSMCs, whereas knockdown of SM22α 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 SM22α expression, inhibition of ROS generation and ERK phosphorylation were, at least, partly responsible for the effects of SSHE on VSMCs.

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  • Authors+Show Affiliations

    ,

    The Forth Affiliated Hospital of Hebei Medical University, No. 12 Health Road, Shijiazhuang 050011, PR China. Electronic address: lijiankunvp@163.com.

    ,

    Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: wel_lw@163.com.

    ,

    Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 11277038@qq.com.

    ,

    Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: lilizhao2008@126.com.

    ,

    Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 578405341@qq.com.

    ,

    Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 1434214904@qq.com.

    ,

    Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 948931336@qq.com.

    Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, PR China. Electronic address: 597654544@qq.com.

    Source

    Journal of ethnopharmacology 235: 2019 May 10 pg 155-163

    MeSH

    Animals
    Becaplermin
    Carotid Intima-Media Thickness
    Cell Movement
    Cell Proliferation
    Chromatography, High Pressure Liquid
    Dose-Response Relationship, Drug
    Male
    Mice
    Mice, Inbred C57BL
    Muscle, Smooth, Vascular
    Myocytes, Smooth Muscle
    Plant Extracts
    Rats
    Scutellaria
    Tandem Mass Spectrometry

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30763696

    Citation

    Li, Jiankun, et al. "Anti-proliferative and Anti-migratory Effects of Scutellaria Strigillosa Hemsley Extracts Against Vascular Smooth Muscle Cells." Journal of Ethnopharmacology, vol. 235, 2019, pp. 155-163.
    Li J, Wang H, Shi X, et al. Anti-proliferative and anti-migratory effects of Scutellaria strigillosa Hemsley extracts against vascular smooth muscle cells. J Ethnopharmacol. 2019;235:155-163.
    Li, J., Wang, H., Shi, X., Zhao, L., Lv, T., Yuan, Q., ... Zhu, J. (2019). Anti-proliferative and anti-migratory effects of Scutellaria strigillosa Hemsley extracts against vascular smooth muscle cells. Journal of Ethnopharmacology, 235, pp. 155-163. doi:10.1016/j.jep.2019.02.016.
    Li J, et al. Anti-proliferative and Anti-migratory Effects of Scutellaria Strigillosa Hemsley Extracts Against Vascular Smooth Muscle Cells. J Ethnopharmacol. 2019 May 10;235:155-163. PubMed PMID: 30763696.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Anti-proliferative and anti-migratory effects of Scutellaria strigillosa Hemsley extracts against vascular smooth muscle cells. AU - Li,Jiankun, AU - Wang,Hairong, AU - Shi,Xiaowei, AU - Zhao,Lili, AU - Lv,Tao, AU - Yuan,Qi, AU - Hao,Wenyang, AU - Zhu,Jing, Y1 - 2019/02/11/ PY - 2018/11/15/received PY - 2019/01/30/revised PY - 2019/02/09/accepted PY - 2019/2/15/pubmed PY - 2019/4/16/medline PY - 2019/2/15/entrez KW - Anti-migration KW - Anti-proliferative KW - Neointima hyperplasia KW - Scutellaria strigillosa Hemsley KW - VSMCs SP - 155 EP - 163 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 235 N2 - 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 SM22α was significantly elevated in SSHE-pretreated VSMCs, whereas knockdown of SM22α 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 SM22α expression, inhibition of ROS generation and ERK phosphorylation were, at least, partly responsible for the effects of SSHE on VSMCs. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/30763696/Anti-proliferative_and_anti-migratory_effects_of_Scutellaria_strigillosa_Hemsley_extracts_against_vascular_smooth_muscle_cells L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(18)34247-8 DB - PRIME DP - Unbound Medicine ER -