Planta Med 2002; 68(7): 605-609
DOI: 10.1055/s-2002-32901
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Effects of Apigenin on the Serum- and Platelet Derived Growth Factor-BB-Induced Proliferation of Rat Aortic Vascular Smooth Muscle Cells

Tack-Joong Kim1, 2 , Yong-He Zhang3 , Youngsoo Kim1, 2 , Chong-Kil Lee1, 2 , Myung-Koo Lee1, 2 , Jin-Tae Hong1 , Yeo-Pyo Yun1, 2
  • 1College of Pharmacy, Chungbuk National University, Cheongju, Korea
  • 2Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea
  • 3Department of Pharmacology, Peking University, The School of Basic Medical Science, Beijing, China
Further Information

Publication History

Received: October 19, 2001

Accepted: February 3, 2002

Publication Date:
22 July 2002 (online)

Abstract

The inhibitory effects of apigenin on the growth factor-induced proliferative responses, and expression of mitogen-activated protein (MAP) kinase and its downstream c-fos in rat aortic vascular smooth muscle cells (VSMCs) were investigated. Apigenin significantly inhibited both 5 % fetal bovine serum (FBS)- and 50 ng/mL platelet derived growth factor-BB (PDGF-BB)-induced proliferation on primary cultured rat VSMCs in a concentration-dependent manner. In addition, apigenin resulted in a significant inhibition of the FBS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and expression of c-fos mRNA. These results suggest that apigenin inhibits FBS- and PDGF-BB-induced VSMC proliferation, and its activity may be mediated, at least in part, by down regulation of ERK 1/2 and its downstream c-fos mRNA.

References

  • 1 Ross R. The pathogenesis of arteriosclerosis: An update.  New England Journal of Medicine. 1986;  314 488-500
  • 2 Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990’s.  Nature. 1993;  362 801-9
  • 3 Davis R J. The mitogen-activated protein kinase signal transduction pathway.  Journal of Biological Chemistry. 1993;  268 14 553-6
  • 4 Lewis N G. Plant Phenolics. Antioxidants in Higher Plants. In: Alscher RG, Hess JL, editors CRC Press Boca Raton, FL; 1993: 135-69
  • 5 Ji Y B. Pharmacological action and application of blood activating and stasis-eliminating available composition of Traditional Chinese Medicine. Publishing House of Sci Tech HeilongJiang China; 1999: 22
  • 6 Gerritsen M E, Carley W W, Ranges G E, Shen C P, Phan S A, Ligon G F . et al . Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression.  American Journal of Pathology. 1995;  147 278-92
  • 7 Capasso A, Pinto A, Sorrentino R, Capasso F. Inhibitory effects of quercetin and other flavonoids on electrically-induced contractions of guinea pig isolated ileum.  Journal of Ethnopharmacology. 1991;  34 279-81
  • 8 Di Carlo G, Autore G, Izzo A A, Maiolino P, Mascolo N, Viola P . et al . Inhibition of intestinal motility and secretion by flavonoids in mice and rats: Structure-activity relationships.  Journal of Pharmacy and Pharmacology. 1993;  45 1054-9
  • 9 Chamley-Campbell J, Campbell G R, Ross R. The smooth muscle cell in culture.  Physiological Reviews. 1979;  59 1-61
  • 10 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.  Analytical Biochemistry. 1987;  162 156-9
  • 11 Lau K M, Leav I, Ho S M. Rat estrogen receptor-α and -β, and progesterone receptor mRNA expression in various prostatic lobes and microdissected normal and dysplastic epithelial tissues of the noble rats.  Endocrinology. 1998;  139 424-7
  • 12 Curran T, Gordon M B, Rubino K L, Sambucetti L C. Isolation and characterization of the c-fos (rat) cDNA and analysis of post-transcriptional modification in vitro .  Oncogene . 1987;  2 79-84
  • 13 Fort P, Marty L, Piechaczyk M, Sabroutys D C, Jeanteur P, Blanchard J M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate dehydrogenase multigenic family.  Nucleic Acids Research. 1985;  13 1431-42
  • 14 Ohlstein E H, Douglas S A, Sung C P, Yue T L, Louden C, Arleth A . et al . Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury.  Proceedings of National Academy of Sciences of the USA. 1993;  90 6189-93
  • 15 Ahn H Y, Hadizadeh K R, Seul C, Yun Y P, Vetter H, Sachinidis A. Epigallocatechin 3-gallate selectively inhibits the PDGF-BB-induced intracellular signaling transduction pathway in vascular smooth muscle cells and inhibits transformation of sis-transfected NIH 3T3 fibroblasts and human glioblastoma cells (A172).  Molecular Biology of the Cell. 1999;  10 1093-104
  • 16 Zhang Y H, Park Y S, Kim T J, Fang L H, Ahn H Y, Hong J T . et al .Endothelium-dependent vasorelaxant and antiproliferative effects of apigenin. General Pharmacology 2002 35: 341-7
  • 17 Wennstrom S, Siegbahn A, Yokote K. Membrane ruffling and chemotaxis transduced by the PDGF beta-receptor require the binding site for phosphatidylinositol 3-kinase.  Oncogene. 1994;  9 651-60
  • 18 Agullo G, Gamet-Payrastre L, Manenti S, Viala C, Remesy C, Chap H . et al . Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition.  Biochemical Pharmacoloy.. 1997;  53 1649-57

Yeo-Pyo Yun, Ph. D., Professor 

College of Pharmacy

Chungbuk National University

48 Gaesin-Dong, Heungduk-Gu

Cheongju, 361-763

Republic of Korea

Email: ypyun@cbucc.chungbuk.ac.kr

Fax: +82-43-268-2732

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