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.
Department of Anesthesia, China Medical University and Hospital, Taichung, Taiwan, ROC.
Kar-Lok
KL
Wong
Jia-Wei
JW
Lin
Ju-Chi
JC
Liu
Hung-Yu
HY
Yang
Pei-Feng
PF
Kao
Cheng-Hsien
CH
Chen
Shih-Hurng
SH
Loh
Wen-Ta
WT
Chiu
Tzu-Hurng
TH
Cheng
Jaung-Geng
JG
Lin
Hong-Jye
HJ
Hong
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