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KMID : 0043320160390020249
Archives of Pharmacal Research
2016 Volume.39 No. 2 p.249 ~ p.258
Cryptotanshinone and wogonin up-regulate eNOS in vascular endothelial cells via ER¥á and down-regulate iNOS in LPS stimulated vascular smooth muscle cells via ER¥â
Oche Barnabas

Chen Lu
Ma Ya ke
Yang Yue
Li Chun xiao
Geng Xiao
Qiu Li zhen
Gao Xiu mei
Wang Hong
Abstract
Phytoestrogens were widely used as natural alternatives to estrogen for treating cardiovascular diseases. They have been reported to have cardioprotective and anti-inflammatory response, but the mechanisms remain unclear. In this study, we found cryptotanshinone and wogonin exhibited phytoestrogenic property in an estrogen-responsive reporter assay. In EA.hy926 cells, treatment of cryptotanshinone and wogonin led to significant increase in NO production levels, which were inhibited by co-incubation of estrogen receptor (ER)¥á antagonist methyl-piperidino-pyrazole (MPP). The expression of endothelial NO synthase (eNOS) and ER¥á were up-regulated with the same treatment, indicating they stimulate NO and eNOS expression via ER¥á-dependent pathway in endothelial cells. While in lipopolysaccharide activated vascular smooth muscle cell line A7r5, cryptotanshinone and wogonin exerted anti-inflammatory effects by inhibiting NO and inducible NO synthase expression via ER¥â-dependent pathway. The reduction of NO synthesis was not affected by MPP, and was abrogated by ER¥â antagonist R,R-tetrahydrochrysene. Our findings provide the potential molecular mechanism of cryptotanshinone and wogonin as phytoestrogens for their cardioprotective effects, which exerted regulatory effects on NO synthesis through differential regulation of estrogen receptors. It can be employed as a basis for evaluating the beneficial effects of phytoestrogens in the treatment of patients at risk of cardiovascular disease.
KEYWORD
Phytoestrogens, Cryptotanshinone, Wogonin, Estrogen receptors, Nitric oxide synthase, Cardiovascular disease
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