Abstract
The abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Preincubation of the VSMCs with L7G significantly inhibited the PDGF-BB- induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C (PLC)-λ1 activation. However, L7G had almost no affect on the phosphorylation of PDGF-β receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCsvia the blocking of PLC-γ1, Akt, and ERK1/2 phosphorylation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Casagrande, F. and Darbon, J. M., Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1.Biochem. Pharmacol., 61, 1205–1215 (2001).
Chamley, J. H., Campbell, G. R., McConnell, J. D., and Groschel-Stewart, U., Comparison of vascular smooth muscle cells from adult human, monkey and rabbit in primary culture and in subculture.Cell Tissue Res., 177, 503–522 (1977).
Chen, Y. T., Zheng, R. L., Jia, Z. J., and Ju, Y., Flavonoids as superoxide scavengers and antioxidants.Free Radic. Biol. Med., 9, 19–21 (1990).
Claesson-Welsh, L., Platelet-derived growth factor receptor signals.J. Biol. Chem., 269, 32023–32026 (1994).
Graf, K., Xi, X. P., Yang, D., Fleck, E., Hsueh, W. A., and Law, R. E., Mitogen-activated protein kinase activation is involved in platelet-derived growth factor-directed migration by vascular smooth muscle cells.Hypertension 29, 334–339 (1997).
Lu, H. W., Sugahara, K., Sagara, Y., Masuoka., N., Asaka, Y., and Manabe. M., Effect of three flavonoids, 5,7,3,4-tetrahydroxy-3-methoxy flavone, luteolin, and quercetin, on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophil.Arch. Biochem. Biophys., 393, 73–77 (2001).
Kim, T. J., Zhang, Y. H., Kim, Y., Lee, C. K., Lee, M. K., Hong, J. T., and Yun, Y. P., Effects of apigenin on the serum- and platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells.Planta Med., 68, 605–609 (2002).
Majesky, M. W., Reidy, M. A., Bowen-Pope, D. F., Hart, C. E., Wilcox, J. N., and Schwartz, S. M., PDGF ligand and receptor gene expression during repair of arterial injury.J. Cell. Biol., 111, 2149–2158 (1990).
Mulvany, M. J., Structure and function of small arteries in hypertension.J. Hypertens. Suppl., 8, 225–232 (1990).
Ohlstein, E. H., Douglas, S. A., Sung, C. P., Yue, T. L., Louden, C., and Arleth, A., Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury.Proc. Natl. Acad. Sci. U.S.A., 90, 6189–6193 (1993).
Ross, R., Mechanisms of atherosclerosis-a review.Adv. Nephrol. Necker. Hosp., 19, 79–86 (1990).
Ross, R., Cell biology of atherosclerosis.Annu. Rev. Physiol., 57, 791–804 (1995).
Sachinidis, A., Locher, R., Vetter, W., Tatje, D., and Hoppe, J., Different effects of platelet-derived growth factor isoforms on rat vascular smooth muscle cells.J. Biol. Chem., 265, 10238–10243 (1990).
Shimoi, K., Okada, H., Furugori, M., Goda, T., Takase, S., and Suzuki, M., Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans.FEBS Lett., 438, 220–224 (1998).
Shimoi, K., Saka, N., Kaji, K., Nozawa, R., and Kinae, N., Metabolic fate of luteolin and its functional activity at focal site.Biofactors, 12, 181–186 (2000).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kim, TJ., Kim, JH., Jin, YR. et al. The inhibitory effect and mechanism of luteolin 7-glucoside on rat aortic vascular smooth muscle cell proliferation. Arch Pharm Res 29, 67–72 (2006). https://doi.org/10.1007/BF02977471
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02977471