Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, which is commonly used as a noncaloric sugar substitute in Japan and Brazil. The aims of this study were to examine whether isosteviol alters angiotensin-II-induced cell proliferation in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with isosteviol, then stimulated with angiotensin II, after which [3H]thymidine incorporation and endothelin-1 secretion were examined. Isosteviol (1-100 μmol/l) inhibits angiotensin-II-induced DNA synthesis and endothelin-1 secretion. Measurements of 2′7′-dichlorofluorescin diacetate, a redox-sensitive fluorescent dye, showed an isosteviol-mediated inhibition of intracellular reactive oxygen species generated by the effects of angiotensin II. The inductive properties of angiotensin II on extracellular signal-regulated kinase (ERK) phosphorylation were found reversed with isosteviol and antioxidants such as N-acetylcysteine. In summary, we speculate that isosteviol inhibits angiotensin-II-induced cell proliferation and endothelin-1 secretion via attenuation of reactive oxygen species generation. Thus, this study provides important insights that may contribute to the effects of isosteviol on the cardiovascular system.
ASJC Scopus subject areas
Wong, K. L., Lin, J. W., Liu, J. C., Yang, H. Y., Kao, P. F., Chen, C. H., Loh, S. H., Chiu, W. T., Cheng, T-H., Lin, J. G., & Hong, H. J. (2006). Antiproliferative effect of isosteviol on angiotensin-II-treated rat aortic smooth muscle cells. Pharmacology, 76(4), 163-169. https://doi.org/10.1159/000091417