Antiproliferative effect of isosteviol on angiotensin-II-treated rat aortic smooth muscle cells.
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 [(3)H]thymidine incorporation and endothelin-1 secretion were examined. Isosteviol (1-100 micromol/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.
Wong
Kar-Lok
KL
Department of Anesthesia, China Medical University and Hospital, Taichung, Taiwan, ROC.
Lin
Jia-Wei
JW
Liu
Ju-Chi
JC
Yang
Hung-Yu
HY
Kao
Pei-Feng
PF
Chen
Cheng-Hsien
CH
Loh
Shih-Hurng
SH
Chiu
Wen-Ta
WT
Cheng
Tzu-Hurng
TH
Lin
Jaung-Geng
JG
Hong
Hong-Jye
HJ
D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000096:biosynthesis; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013549:Sweetening Agents / Q000494:pharmacology*
D045786:Diterpenes, Kaurane; D019332:Endothelin-1; D017382:Reactive Oxygen Species; D013549:Sweetening Agents; D000804:Angiotensin II; C012042:steviol