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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells.

OBJECTIVES: To investigate the effect of icariin on the cyclic guanosine monophosphate (cGMP)-hydrolytic activity of phosphodiesterase-5 (PDE5) isoforms and the cGMP levels in cavernous smooth muscle cells treated with sodium nitroprusside (SNP). METHODS: PDE5 isoforms (PDE5A1, A2, and A3) were isolated from sf9 insect cells infected with baculoviruses carrying PDE5 isoform cDNA. Icariin was isolated from Epimedii herba. Varying amounts (10(-6) to 10(-11) M) of icariin or zaprinast were added to reaction mixtures containing PDE5 isoforms and cGMP. The inhibitory effects of icariin and zaprinast were analyzed by GraphPad Software and are expressed as concentration that inhibits 50% (IC(50)) values. Cavernous smooth muscle cells were isolated from 3-month-old rats, treated with icariin (100 and 200 muM) or zaprinast (200 muM) for 15 minutes, and then with 10 muM SNP for 30, 60, 120, 240, and 360 minutes. The cells were then analyzed for the cGMP concentration using an enzyme immunoassay system. RESULTS: Icariin inhibited PDE5A1, A2, and A3 with an IC(50) value of 1.0, 0.75, and 1.1 muM, respectively. The corresponding IC(50) values for zaprinast were 0.33, 0.23, and 0.32 muM. Icariin consistently outperformed the control (SNP-only treatment) in maintaining greater cGMP levels, particularly at the greater concentration of 200 muM. In contrast, zaprinast at 200 muM did better than the control only at 60 and 360 minutes. CONCLUSIONS: Icariin was inhibitory to all three PDE5 isoforms with similar IC(50) values, which were approximately three times greater than those for zaprinast. Icariin was able to enhance cGMP levels in SNP-treated cavernous smooth muscle cells.[1]

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