Antioxidative mechanism of Lycium barbarum polysaccharides promotes repair and regeneration following cavernous nerve injury

Polysaccharides extracted from Lycium barbarum exhibit antioxidant properties.We hypothesized that these polysaccharides resist oxidative stress-induced neuronal damage following cavernous nerve injury.In this study,rat models were intragastrically administered Lycium barbarum polysaccharides for 2 weeks at 1,7,and 14 days after cavernous nerve injury.Serum superoxide dismutase and glutathione peroxidase activities significantly increased at 1 and 2 weeks post-injury.Serum malondialdehyde levels decreased at 2 and 4 weeks.At 12 weeks,peak intracavernous pressure,the number of myelinated axons and nicotinamide adenine dinucleotide phosphate-diaphorase-positive nerve fibers,levels of phospho-endothelial nitric oxide synthase protein and 3-nitrotyrosine were higher in rats administered at 1 day post-injury compared with rats administered at 7 and 14 days post-injury.These findings suggest that application of Lycium barbarum polysaccharides following cavernous nerve crush injury effectively promotes nerve regeneration and erectile functional recovery.This neuroregenerative effect was most effective in rats orally administered Lycium barbarum polysaccharides at 1 day after cavernous nerve crush injury.

Animal models for studying penile hemodynamics

Animal models for the study of erectile function monitoring the changes in intracavernous pressure (ICP) during penile erection was reviewed. The development of new models using small commercially-available experimental animals, rats and mice, in the last decade facilitated in vivo investigation of erectile physiology. The techniqueenabled to evaluate even subtle erectile responses by analyzing ICP and systemic blood pressure. Moreover, the method has been well improved and studies using conscious animal models without the influence of any drug or anesthesia are more appropriate in exploring the precise physiological and pharmacological mechanisms in erection. Also, more natural and physiological sexual arousal instead of electrical or pharmacological stimulation is desirable in most of the studies.This article reviewed the development of ICP studies in rats and mice.

Erectile potentials of a new phosphodiesterase type 5 inhibitor,DA-8159,in diet-induced obese rats

Aim:To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159,a new phosphodiesterase type 5(PDE5)inhibitor,on penile erection in obese rats.Methods:The rats were fed a high-energy diet for 12 weeks and divided into three groups:an obesity-resistant(OR)control group,an obesity- prone(OP)control group,and an OP-DA-8159 treatment(DA-8159)group.The electrostimulation-induced erectile responses were measured in all groups.The body weight,plasma cholesterol,triglyceride and glucose levels were also measured.Results:In the OP control group,the maximum intracavernous pressure(ICP)and ICP/blood pressure(ICP/BP)ratio after electric stimulation were significantly lower than those in OR control group.The corresponding area under the curve(AUC)of the ICP/BP ratio,the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group,but this difference was not significant.The body weight gain,plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159,a significant increase in the maximum ICP and the ICP/BP ratio were observed.The coerrsponding AUCs in the DA-8159 group were also higher than those in the two control groups.Furthermore,the detumescence time was significantly prolonged after treatment with DA-8159.Conclusion:These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction(ED)can be im- proved by the treatment with DA-8159,indicating DA-8159 might be a treatment option for ED associated with obesity.

Pancreatic kininogenase improves erectile function in streptozotocin-induced type 2 diabetic rats with erectile dysfunction

Erectile dysfunction （ED） associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase （PK） has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate （cGMP） levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.

A new therapeutic approach to erectile dysfunction： urotensin-II receptor high affinity agonist ligands

Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure （ICP） in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U （H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH） and UPG84（H-Asp-c[Pen-Phe-DTrp-Orn-（pNH2） Phe-Cys]-Val-OH）. The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II （0.03-1 nmol）, P5U （0.03-1 nmol） or UPG84 （0.03-1 nmol） caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose （0.03 nmol） showed an effect similar to the highest dose of U-II （1 nmol）. Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U （0.03 nmol） did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.