Effect of α-asarone on angiogenesis and matrix metalloproteinase.

α-Asarone is a main component of Acorus gramineus widely known as an oriental traditional medicinal stuff. A. gramineus has been known to have a variety of medicinal efficacies such as anti-gastric ulcer and anti-allergic activities, inhibition of histamine release and antioxidant effect. However, its effect on angiogenesis remains unclear. The aim of this study was to investigate the effect of α-asarone on induction of angiogenesis through modulation of matrix metalloproteinase (MMP). First of all, MTT assay was performed to evaluate the effect of α-asarone on cell viability using MTT assay, and then tube formation assay with human umbilical vein endothelial cells (HUVEC) in vitro and rat aorta ring assay ex vivo were carried out to elucidate its effect on angiogenesis. Treatment with α-asarone below 6μM showed no cytotoxicity in human fibrosarcoma cells (HT1080) and HUVEC. It was observed that α-asarone not only promotes tube formation of HUVEC but also induces angiogenesis of rat aorta. In addition, the effects of α-asarone on the expressions of protein and gene were evaluated using western blot analysis and RT-PCR assay. α-Asarone increased the expression levels of MMP-2 and MMP-9 stimulated by phenazine methosulfate (PMS) and phorbol 12-myristate 13-acetate (PMA) in HT1080. Especially, the expression level of antioxidant enzyme such as glutathione reductase was increased in the presence of α-asarone. Therefore, above findings suggest that α-asarone may play an important role in pathological diseases related to MMP and angiogenesis.