Impact of cirsivm japonicum De Candol on plasminogen activator system in cultured vascular smooth muscle cells

Abstract

OBJECTIVE: To avoid possible adverse effects of hormone therapy such as breast cancer and cardiovascular disease, the use of alternatives in postmenopausal women is substantially increasing. Cirsivm japonicum De Candol (C. japonicum) has long been used to manage menopause-related symptoms and treat cardiovascular disease in Korea. However, despite of its wide clinical use, there is limited knowledge of its mechanisms of action or efficacy. This study was performed to investigate the direct impact of C. japonicum on plasminogen activator system of vascular smooth muscle cells (VSMC) from rat aorta. DESIGN: To examine the effects of an aqueous extract of C. japonicum on plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) in rat VSMC. MATERIALS AND METHODS: VSMC were derived from 3-month-old female Sprague-Dawley rat aorta, using enzyme digestion method. Cells stained positively for α-smooth muscle actin. Expressions of PAI-1 and t-PA were assessed with Western blot analyses and zymography. Impacts of C. japonicum alone and C. japonicum combined with lysoPC, an active component of oxidized low-density lipoprotein, were studied. Mann-Whitney test and Wilcoxon rank sum test were applied for statistical analysis. RESULTS: C. japonicum alone had no effect on PAI-1 and t-PA expression (n=5, respectively). LysoPC stimulated PAI-1 expressions via increased oxidative stress (n=5), but did not affect t-PA in VSMC (n=5). C. japonicum (50∼400 μg/ml) suppressed PAI-1 expression induced with lysoPC (10 μg/ml, 4hr) in a dose-dependent manner (n=5). CONCLUSIONS: C. japonicum inhibits PAI-1 expression induced by lysoPC. This traditional herbal medicine might play a role as an estrogen alternative and have beneficial effects on cardiovascular system. Further study is needed to evaluate the effectiveness as a complementary and alternative medicine.