The aim of this study was to explore the effects and mechanisms of Icarisid II (ICA-II) on enhancing the cellular cGMP in rat corpus cavernosum tissue (RCCT). Diabetes mellitus Wistar rats were induced by streptozotocin, and diabetic ED rats were selected for the RCCT culture by apomorphine. ICA-II was extracted and purified from Icariin (ICA) by enzymatic method. The RCCT was treated with ICA-II, ICA and Sildenafil at different concentrations. cGMP and nitric oxide synthase (NOS) activities were checked respectively by enzyme immunoassay. Meanwhile, nNOS, iNOS and eNOS in RCCT were checked by western blot. ICA-II evaluated the intracellular cGMP to 8.01 ± 1.02 pmol mg(-1) min(-1), which is much weaker than that from Sildenafil (12.4 ± 1.16 pmol mg(-1) min(-1)) (P < 0.05). There is no significant difference between ICA-II and ICA. With the treatment of 10 μm ICA-II for 24 and 48 h, nNOS expression was significantly increased in RCCT (P < 0.05), while the eNOS expression level was very low without any change. Notably, ICA-II increased the intracellular NOS activity significantly in vitro in RCCT. Except the PDE5 inhibitory effect, ICA-II increases the intracellular cGMP through the enhancement of nNOS expression and NOS activity in RCCT in vitro. ICA-II implies a potential compound for neurogenic erectile dysfunction by NO-cGMP pathway.
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