sildenafil-citrate and icariin

The commonly utilized phosphodiesterase type 5 inhibitors do not lead to satisfactory penile erection after radical prostatectomy mainly because of insufficient nitric oxide drive from the damaged cavernous nerves. The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (50 mg/kg) at postnatal day 1 for the purpose of tracking endogenous stem cells in penis. Forty-eight rats of bilateral cavernous nerves injury were randomized equally into gavage feeding of vehicle, sildenafil (10 mg/kg), icariin (1.5 mg/kg) and sildenafil + icariin, respectively. Twelve sham-operated rats served as control. The intracavernous pressure and mean arterial pressure was measured and mid-penile cross sections were histologically examined 5 weeks after surgery. Western blotting of cavernous tissue protein was also performed. Animals treated with sildenafil + icariin had significantly higher mean intracavernous pressure/mean arterial pressure ratio relative to other rats with bilateral cavernous nerves injury (p < 0.05). The circumference and mean cross-sectional area of the paired corpus cavernosum were effectively preserved in the sildenafil + icariin. Treatment with sildenafil + icariin significantly increased the cavernous cyclic guanosine monophosphate concentration compared with the icariin group (p < 0.05). In addition, the numbers of neuronal nitric oxide synthase-positive nerves and 5-ethynyl-2-deoxyuridine-positive cells co-expressing S100 in the icariin-treated groups were greater compared with the bilateral cavernous nerves injury control group (p < 0.05). These data suggest that the combined use of icariin and daily sildenafil holds promise as a potential therapy for neurogenic erectile dysfunction in the future. The underlying mechanisms appears to involve two aspects: (i) icariin promotes differentiation of endogenous stem cells to Schwann cells, which help to repair the damaged neural pathway for erection; (ii) on this basis, sildenafil can further improve penile engorgement through the cyclic guanosine monophosphate-dependent smooth muscle relaxation.

Topics: Animals; Atrophy; Blotting, Western; Disease Models, Animal; Erectile Dysfunction; Flavonoids; Fluorescent Antibody Technique; Male; Penile Erection; Penis; Prostatectomy; Rats; Rats, Sprague-Dawley; Sildenafil Citrate

Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium brevicornum, Cinnamomum cassia), and the individual compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. brevicornum extract (80% inhibition at 50 microg/mL) and its active principle icariin (1) (IC50 5.9 microM) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development.

Topics: Cyclic Nucleotide Phosphodiesterases, Type 6; Epimedium; Erectile Dysfunction; Ferula; Flavonoids; Humans; Inhibitory Concentration 50; Male; Molecular Structure; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Plant Extracts; Purines; Sildenafil Citrate; Structure-Activity Relationship; Sulfones; Tribulus

To realize the effect of icariin on erectile function of penis.. After the cavernous nerve (CN) of rat was isolated unilaterally, the corpora cavernosa (CC) and right carotid artery were exposed. A 26G needle catheter was inserted into the right CC to monitor the intracavernous pressure (ICP), and another 26G needle catheter was inserted into the left CC for drug administration. Another catheter was placed into the carotid artery to monitor mean systematic arterial blood press (MBp). Icariin of different concentrations was administrated intracavernosally, and the ICP and MBp were recorded during electric stimulation on CN. Sildenafil and papaveine were used as controls. The effects of nitric oxide syntheses (NOS) inhibitor N(omega)-nitro-L-arginine (LNNA), and soluble guanylate cyclase inhibitor H-[1,2,4] oxadiazolo [4,3,-a] quinoxalin-1-one (ODQ) on icariin (10(-4)mol/L) induced ICP changes were investigated also.. Icariin, sidenafil and papaverine increased the ICP in a dose-depended manner (P < 0.01). Icariin and sildenafil did not influence the MBp (P > 0.05), however, papaverine significant influenced MBp (P < 0.01). EC(50) of Icariin, sildenafil and papaveine on ICP/MBp were 2.23 micro mol/L, 0.24 micro mol/L and 9.73 micro mol/L respectively. ODQ and LNNA significantly decreased ICP induced by icariin (10(-4)mol/L).. Icariin increases ICP without influence on MBp and such effect is inhibited by LNNA and ODQ significantly. Icariin regulates the activity of NO-cGMP signal pathway on CC to enhance erectile function by oral therapy.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Female; Flavonoids; Nitroarginine; Oxadiazoles; Papaverine; Penile Erection; Piperazines; Pressure; Purines; Quinoxalines; Rats; Rats, Wistar; Sildenafil Citrate; Sulfones