Inhibitory role of magnolol on proliferative capacity and matrix metalloproteinase-9 expression in TNF-α-induced vascular smooth muscle cells

Hong Man Kim, Sung Jin Bae, Dong Wook Kim, Bo Kyung Kim, Soo Bok Lee, Ung Soo Lee, Cheorl Ho Kim, Sung Kwon Moon

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Magnolol, an active component extracted from Magnolia officinalis, has been reported to inhibit the development of atherosclerotic disease. However, it is not known whether magnolol exerts similar cardioprotective effects in cells treated with TNF-α. In the present study, magnolol treatment was found to show potent inhibitory effects on cell proliferation in cultured VSMC in the presence of TNF-α. These inhibitory effects were associated with reduced extracellular signal-regulated kinase (ERK) 1/2 activity and G1 cell cycle arrest. Magnolol treatment strongly induced the expression of p21WAF1, but resulted in a decrease in cyclin-dependent kinases (CDKs) and cyclins involved in G1 progression. In addition to G1 cell cycle arrest and growth inhibition in VSMC, magnolol also caused the strong inhibition of TNF-α-induced matrix metalloproteinase-9 (MMP-9) expression in a dose-dependent manner as determined by zymography and immunoblot. Moreover, magnolol treatment strongly decreased MMP-9 promoter activity in response to TNF-α. We further demonstrated that magnolol reduced the transcriptional activity of NF-κB and activation protein-1 (AP-1), two important nuclear transcription factors that are involved in MMP-9 expression. Collectively, these results show that magnolol inhibits cell proliferation, G1 to S phase cell cycle progress and MMP-9 expression through the transcription factors NF-κB and AP-1 in TNF-α-induced VSMC. The findings of the present study reveal a potential mechanism that explains the anti-atherogenic activity of magnolol.

Original languageEnglish
Pages (from-to)1083-1091
Number of pages9
JournalInternational Immunopharmacology
Volume7
Issue number8
DOIs
Publication statusPublished - 2007 Aug

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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