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Icariin exhibits inhibitory effects on cGMP-specific phosphodiesterase PDE5 and cAMP-specific phosphodiesterase PDE4 activities. Phosphodiesterase (PDE) is a crucial regulator of cAMP/PKA signaling. PDEs are encoded by 21 genes which can be sdivided into 11 families according to the substrate specificities and subcellular localization. PDEs are widely expressed in neurons. PDE5 has been implicated in regulating some physiological processes such as smooth muscle relaxation and neuronal survival. PDE4 has been associated with the DARPP-32 signaling pathway and dopaminergic neurotransmission [1].

In vitro: Icariin inhibited the activity of PDE5 and PDE4 in a dose- andconcentration-dependent manner. The IC50of icariin on PDE5 was 0.43 μM and the IC50 on PDE4 was 73.50 μM. Icariin showed a selective inhibitory effect on cGMP-specific PDE5 compared to cAMP-specific PDE4 [2].Icariincould also enhance the osteogenic differentiation of rat primary bone marrow stromal cells [3].

In vivo: In castrated rats, a 4-week oral administration of icariinat 1 mg/kg/day and 5 mg/kg/day improved the erectile function and increased nNOS and iNOS expression [4].Icariin also showed its effect on stimulating angiogenesis in human endothelial cells [5].

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