사람 동맥 평활근 세포에 대한 Rosmarinic Acid의 항동맥경화 활성
Anti-Atherosclerosis Activity of Rosmarinic Acid in Human Aortic Smooth Muscle Cells
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Rosmarinic acid frequently found as a secondary metabolite in herbs and medicinal plants, has exhibited antimicrobial, antiviral, antioxidative, and anti-inflammatory activities. The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Rosmarinic acid on the proliferation and migration of HASMC. Rosmarinic acid suppressed the proliferation of HASMC via induction of the expression of apoptotic proteins including cleaved poly ADP-ribose polymerase (PARP), and caspase-3. Rosmarinic acid decreased anti-apoptotic Bcl-2 and increased pro-apoptotic Bax. Moreover, treatment of rosmarinic acid decreased the G1/S cycle regulation proteins (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and increased p21, p27 and p53. Rosmarinic acid also blocked HASMC migration via suppression of MMP-9 and MMP-2. Taken together, these results indicate that rosmarinic acid has the potential for use as an anti-atherosclerosis agent.
Abstract
Rosmarinic acid frequently found as a secondary metabolite in herbs and medicinal plants, has exhibited antimicrobial, antiviral, antioxidative, and anti-inflammatory activities. The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Rosmarinic acid on the proliferation and migration of HASMC. Rosmarinic acid suppressed the proliferation of HASMC via induction of the expression of apoptotic proteins including cleaved poly ADP-ribose polymerase (PARP), and caspase-3. Rosmarinic acid decreased anti-apoptotic Bcl-2 and increased pro-apoptotic Bax. Moreover, treatment of rosmarinic acid decreased the G1/S cycle regulation proteins (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and increased p21, p27 and p53. Rosmarinic acid also blocked HASMC migration via suppression of MMP-9 and MMP-2. Taken together, these results indicate that rosmarinic acid has the potential for use as an anti-atherosclerosis agent.
참고문헌 (27)
- Pirker, K.F., "Free radical generation in rosmarinic acid investigated by electron paramagnetic resonance spectroscopy", Free Radic Res., 43(1), pp.47~57 (2009)
- Fujimoto, A., "Cytometric analysis of cytotoxicity of polyphenols and related phenolics to rat thymocytes: potent cytotoxicity of resveratrol to normal cells", Basic Clin Pharmacol Toxicol., 104(6), pp.455~462 (2009)
- Inoue, K., "Effects of volatile constituents of rosemary extract on lung inflammation induced by diesel exhaust particles", Basic Clin Pharmacol Toxicol., 99(1), pp.52~57 (2006)
- Sanbong,i C., "Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model", Clin Exp Allergy, 34(6), pp.971~977 (2004)
- Lee, J., "Effect of rosmarinic acid on atopic dermatitis", J Dermatol., 35(12), pp.768~771 (2008)
- Swarup, V., "Antiviral and anti-inflammatory effects of rosmarinic acid in an experimental murine model of Japanese encephalitis", Antimicrob Agents Chemother., 51(9), pp.3367~3370 (2007)
- Petersen, M., "Rosmarinic acid", Phytochemistry, 62(2), pp.121~125 (2003)
- Iuvone, T., "The spice sage and its active ingredient rosmarinic acid protect PC12 cells from amyloid-beta peptide-induced neurotoxicity", J Pharmacol Exp Ther., 317(3), pp.1143~1149 (2006)
- Aquilano, K., "Reactive oxygen and nitrogen species are involved in sorbitol-induced apoptosis of human erithroleukaemia cells K562", Free Radic Res., 41(4), pp.452~460 (2007)
- Lin, S.J., "Salvianolic acid B attenuates MMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aortic smooth muscle cells", J Cell Biochem., 100(2), pp.372~384 (2007)
- Desai, A., "Cytotoxicity and apopotosis enhancement in brain tumor cells upon coadministration of paclitaxel and ceramide in nanoemulsion formulations", 97(7), pp.2745~2756 (2008)
- Magaud, J.P., "Detection of human white cell proliferative responses by immunoenzymatic measurement of bromodeoxyuridine uptake", J Immunol Methods., 106(1), pp.95~100 (1988)
- Moon, S.K., "ERK1", 2 mediates TNF-alpha-induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-kappaB and AP-1: Involvement of the ras dependent pathway, 2004, pp.198(3), 417~427
- Moon, S.K., "In vitro cellular aging is associated with enhanced proliferative capacity, G1 cell cycle modulation, and matrix metalloproteinase-9 regulation in mouse aortic smooth muscle cells", Arch Biochem Biophys., 418(1), pp.39~48 (2003)
- Moon, S.K., "Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: role of ERK1", 2,·, Biochem Biophys Res Commun., pp.2003, 301(4)[DOI]
- Zhang, H.S., "Ginsenoside Rg1 inhibits tumor necrosis factor-alpha (TNF-alpha)-induced human arterial smooth muscle cells (HASMCs) proliferation", J Cell Biochem., 98(6), pp.1471~1481 (2006)
- Ross, R., "Cell biology of atherosclerosis", Annu Rev Physiol., 57, pp.791~804 (1995)
- Lee, J., "Rosmarinic acid as a downstream inhibitor of IKK-beta in TNF-alpha-induced upregulation of CCL11 and CCR3", Br J Pharmacol., 148(3), pp.366~375 (2006)
- de Carcer, G., "Targeting cell cycle kinases for cancer therapy", Curr Med Chem., 14(9), pp.969~985 (2007)
- Singh, R.P., "Natural flavonoids targeting deregulated cell cycle progression in cancer cells", Curr Drug Targets., 7(3), pp.345~354 (2006)
- Shukla, S., "Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells", Cell Cycle., 6(9), pp.1102~1114 (2007)
- Gupte, R.S., "Phosphorylation of RIalpha by cyclin-dependent kinase CDK 2", cyclin E modulates the dissociation of the RIalpha-RFC40 complex, 2006, pp.5(6), 653~660
- Sanz-Gonzalez, S.M., "Atheroma development in apolipoprotein E-null mice is not regulated by phosphorylation of p27 (Kip1) on threonine 187", J Cell Biochem., 97(4), pp.735~743 (2006)
- Raffetto, J.D., "Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease", Biochem Pharmacol, 75(2), pp.346~359 (2008)
- Kim, H.J., "Protective role of clusterin", apolipoprotein J against neointimal hyperplasia via antiproliferative effect on vascular smooth muscle cells and cytoprotective effect on endothelial cells, 2009, pp.29(10), 1558~1564
- Bendeck, M.P., "Inhibition of matrix metalloproteinase activity inhibits smooth muscle cell migration but not neointimal thickening after arterial injury", Circ Res., 78(1), pp.38~43 (1996)
- Yong, V.W., "Matrix metalloproteinases and diseases of the CNS", Trends Neurosci., 21(2), pp.75~80 (1998)
