Abstract
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% (IC50) values. Cavernous smooth muscle cells were isolated from 3-month-old rats, treated
with icariin (100 and 200 μM) or zaprinast (200 μM) for 15 minutes, and then with
10 μM 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 IC50 value of 1.0, 0.75, and 1.1 μM, respectively. The corresponding IC50 values for zaprinast were 0.33, 0.23, and 0.32 μM. Icariin consistently outperformed
the control (SNP-only treatment) in maintaining greater cGMP levels, particularly
at the greater concentration of 200 μM. In contrast, zaprinast at 200 μM did better
than the control only at 60 and 360 minutes.
Conclusions
Icariin was inhibitory to all three PDE5 isoforms with similar IC50 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.
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Article info
Publication history
Accepted:
September 13,
2006
Received:
March 10,
2006
Footnotes
This work was supported by the California Urology Foundation, the Rock Foundation, and the National Institutes of Health (grant 2R01-DK-45370).
Identification
Copyright
© 2006 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
