Genistein and Magnolol protect against smooth muscle cell proliferation by upregulating heme oxygenase-1

• Main Authors: Ji-Fang Chen, 陳紀方
• Other Authors: 鄭寶雲
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/39432652889934956524

碩士 === 中國醫藥大學 === 中國藥學研究所碩士班 === 98 === Abstract The isoflavone genistein (4’,5,7-trihydroxyisoflavone) is a dietary-derived natural product present in a variety of plant foods that selectively inhibit the activity of protein-tyrosine kinases. Genistein affects oncogene-induced tumorigenesis, cell proliferation, cell differentiation, angiogenesis, and signal transduction mechanisms activated by growth factors. The multiple effects of genistein in cellular systems are presumed to reflect its ability to inhibit the activity of protein-tyrosine kinase. Magnolol is a major component of Magnolia officinalis, and has been reported to have various biological effects, including anti-carcinogenicity, antioxidant activity, anti-inflammatory and analgesic effects, smooth muscle relaxant activity, and antithrombotic effect. Heme oxygenase-1(HO-1) has emerged recently as a crucial mediator of antioxidant and tissue protective action. Increased HO-1 expression leads to degradation of heme and accumulation of iron, bilirubin, and carbon monoxide (CO). Of these metabolites, bilirubin acts as a direct antioxidant, whereas CO may exert tissue-protective actions primarily through its vasodilator and antiplatelet effects. HO-1 can be induced in vascular smooth muscle cells and endothelial cells and functions as an endogenous inhibitor of vascular smooth muscle cells proliferation. To address the role of HO-1 in the anti-proliferation of genistein, we evaluate the effect of genistein in the expression of HO-1 protein in vascular smooth muscle cells. The results had shown that genistein significantly inhibit the proliferation of vascular smooth muscle cells induced by FBS. Meanwhile, genistein (5, 10, 20 uM) significantly increased the expression of HO-1 protein and the phosphorylation of p44/42 MAPK in vascular smooth muscle cells. Furthermore, it had shown that magnolol (5, 10, 20 uM) had similar effect on the anti-proliferation, the expression of HO-1 protein as well as the activation of p44/42 MAPK in vascular smooth muscle cells. In conclusion, both of genistein and magnolol exert the anti-proliferation effect may associated with the expression of HO-1 and the activation of p44/42 MAPK in vascular smooth muscle cells. Further studies are needed to clarify how genistein and magnolol induced the expression of HO-1 in vascular smooth muscle cells.