Berberine suppresses in vitro migration of human aortic smooth muscle cells through the inhibitions of MMP-2/9, u-PA, AP-1, and NF-κB
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Berberine, a type of isoquinoline alkaloid isolated fromChinese medicinal herbs, has been reported to have variouspharmacological activities. Studies have demonstrated thatberberine has beneficial effects on vascular remodeling andalleviates restenosis after vascular injury. However, itsmechanism of action on vascular smooth muscle cellmigration is not fully understood. We therefore investigatedthe effect of berberine on human aortic smooth muscle cell(HASMC) migration. Boyden chamber assay was performed toshow that berberine inhibited HASMC migration dosedependently. Real-time PCR and Western blotting analysesshowed that levels of matrix metalloproteinase (MMP)-2,MMP-9, and urokinase-type plasminogen activator (u-PA) werereduced by berberine at both the mRNA and protein levels. Western blotting assay further confirmed that activities ofc-Fos, c-Jun, and NF-κB were significantly attenuated. Theseresults suggest that berberine effectively inhibited HASMCmigration, possibly by down-regulating MMP-2, MMP-9, andu-PA; and interrupting AP-1 and NF-κB mediated signaling pathways.
Abstract
Berberine, a type of isoquinoline alkaloid isolated fromChinese medicinal herbs, has been reported to have variouspharmacological activities. Studies have demonstrated thatberberine has beneficial effects on vascular remodeling andalleviates restenosis after vascular injury. However, itsmechanism of action on vascular smooth muscle cellmigration is not fully understood. We therefore investigatedthe effect of berberine on human aortic smooth muscle cell(HASMC) migration. Boyden chamber assay was performed toshow that berberine inhibited HASMC migration dosedependently. Real-time PCR and Western blotting analysesshowed that levels of matrix metalloproteinase (MMP)-2,MMP-9, and urokinase-type plasminogen activator (u-PA) werereduced by berberine at both the mRNA and protein levels. Western blotting assay further confirmed that activities ofc-Fos, c-Jun, and NF-κB were significantly attenuated. Theseresults suggest that berberine effectively inhibited HASMCmigration, possibly by down-regulating MMP-2, MMP-9, andu-PA; and interrupting AP-1 and NF-κB mediated signaling pathways.
참고문헌 (29)
- Mills, B., "Intimal hyperplasia: slow but deadly", Perfusion, 27, pp.520~528 (2012)
- Bennett, M. R., "In-stent stenosis: pathology and implications for the development of drug eluting stents", Heart, 89, pp.218~224 (2003)
- Lowe, H. C., "Coronary in-stent restenosis: current status and future strategies", J. Am. Coll. Cardiol, 39, pp.183~193 (2002)
- Lafont, A., "The smooth muscle cell: sinner or saint in restenosis and the acute coronary syndromes?", J. Am. Coll. Cardiol, 32, pp.283~285 (1998)
- Gerthoffer, W. T., "Mechanisms of vascular smooth muscle cell migration", Circ. Res, 100, pp.607~621 (2007)
- Siefert, S. A., "Matrix metalloproteinases in vascular physiology and disease", Vascular, 20, pp.210~216 (2012)
- Johnson, J. L., "Matrix metalloproteinase (MMP)-3 activates MMP-9 mediated vascular smooth muscle cell migration and neointima formation in mice", Arterioscler. Thromb. Vasc. Biol, 31, pp.30~ (2011)
- Schiller, L. R., "Review article: anti-diarrhoeal pharmacology and therapeutics", Aliment. Pharmacol. Ther, 9, pp.87~106 (1995)
- Hwang, J. -M., "Berberine induces apoptosis through a mitochondria", caspases pathway in human hepatoma cells, 2006, pp.80, 62~73
- Mahata, S., "Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells", Mol. Cancer, 10, pp.39~ (2011)
- Li, X. K., "Huanglian, A chinese herbal extract, inhibits cell growth by suppressing the expression of cyclin B1 and inhibiting CDC2 kinase activity in human cancer cells", Mol. Pharmacol, 58, pp.1287~1293 (2000)
- Nishino, H., "Berberine sulfate inhibits tumor-promoting activity of teleocidin in two-stage carcinogenesis on mouse skin", Oncology, 43, pp.131~134 (1986)
- Pan, G. Y., "The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption", Planta Med, 69, pp.632~636 (2003)
- Leng, S. H., "Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion", Acta Pharmacol. Sin, 25, pp.496~502 (2004)
- Yin, J., "Effects of berberine on glucose metabolism in vitro", Metabolism, 51, pp.1439~1443 (2002)
- Hong, Y., "Effect of berberine on catecholamine levels in rats with experimental cardiac hypertrophy", Life Sci, 72, pp.2499~2507 (2003)
- Hong, Y., "Effect of berberine on regression of pressure-overload induced cardiac hypertrophy in rats", Am. J. Chin. Med, 30, pp.589~599 (2002)
- Zeng, X. H., "Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy", Am. J. Cardiol, 92, pp.173~176 (2003)
- Lee, S., "Berberine inhibits rat vascular smooth muscle cell proliferation and migration in vitro and improves neointima formation after balloon injury in vivo: berberine improves neointima formation in a rat model", Atherosclerosis, 186, pp.29~37 (2006)
- Liang, K. -W., "Berberine suppresses MEK", ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury, 2006, pp.71, 806~817
- Chase, A. J., "Regulation of matrix metalloproteinase (matrixin) genes in blood vessels: a multi-step recruitment model for pathological remodelling", J. Vasc. Res, 40, pp.329~343 (2003)
- Mason, D. P., "Matrix metalloproteinase-9 overexpression enhances vascular smooth muscle cell migration and alters remodeling in the injured rat carotid artery", Circ. Res, 85, pp.1179~1185 (1999)
- Nelson, A. R., "Matrix metalloproteinases: biologic activity and clinical implications", J. Clin. Oncol, 18, pp.1135~1149 (2000)
- Redmond, E. M., "Effect of pulse pressure on vascular smooth muscle cell migration: the role of urokinase and matrix metalloproteinase", Thromb. Haemost, 81, pp.293~300 (1999)
- Bond, M., "Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-κB", FEBS Lett, 435, pp.29~34 (1998)
- Zhang, H. -W., "AP-1 inhibits expression of MMP-2", 9 and its effects on rat smooth muscle cells, 2009, pp.157, e31~e37
- Moon, S. -K., "PTEN induces G1 cell cycle arrest and inhibits MMP-9 expression via the regulation of NF-κB and AP-1 in vascular smooth muscle cells", Arch. Biochem. Biophys, 421, pp.267~276 (2004)
- Suh, S. -J., "Cryptotanshinone from Salvia miltiorrhiza BUNGE has an inhibitory effect on TNF-α-induced matrix metalloproteinase-9 production and HASMC migration via down-regulated NF-κB and AP-1", Biochem. Pharmacol, 72, pp.1680~1689 (2006)
- Shishodia, S., "Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-κB activation through inhibition of IκBα kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1", Carcinogenesis, 24, pp.1269~1279 (2003)
