JTE-013 supplementation improves erectile dysfunction in rats with streptozotocin-induced type ? diabetes through inhibition of Rho?kinase pathway and corporal fibrosis
Considering ED in patients with diabetes had seriously affected the quality of life. However, these patients showed a poor effect rate for the first-line oral phosphodiesterase type 5 (PDE5) inhibitors. Thus, new treatment methods are urgently needed. To investigate whether JTE-013 supplementation could improve diabetes mellitus-induced erectile dysfunction (DMED).
We used 50 male Sprague-Dawley (SD) rats (8-week-old) for the experiment. Of these, 42 were induced Type?DM through the streptozotocin (STZ), and other 8 normal rats constituted the Control group. 8 weeks later, we assessed the erectile function of rats through an apomorphine test. Only rats with DMED were treated with JTE-013 intraperitoneal injection each day for 4 weeks, and other rats were bred in the same condition for 4 weeks.
At 12 weeks after diabetes was induced, fasting glucose concentrations were significantly higher in the DMED group than the other two groups. JTE-013 supplementation could partially reduce the level of fasting glucose. Erectile function in the DMED group was significantly impaired compared with the Control group, and was partially, but significantly, improved in the DMED + JTE-013 group. The DMED group showed the highest level of S1PR2/RhoA/ ROCK/p-MYPT1 signaling pathway activation among all groups, and the DMED + JTE-013 group showed more activation than the Control group. The DMED group showed serious corporal fibrosis, higher level of apoptosis index and expressions of the TGF-?1/ROCK/LIMK2/Cofilin pathway. However, JTE-013 supplementation partially inhibited corporal fibrosis and the apoptosis level, and reduced the activation of these pathways.
JTE-013 supplementation inhibited endothelial dysfunction and corporal fibrosis, leading ultimately to partial improvement of DMED in rats. Our finding provided evidences for a potential treatment method for DMED.