Actions and mechanisms of icariside Ⅱ derivative YS10 in the treatment of erectile dysfunction
ZHU Liang,CAI Qi-liang,XIN Zhong-cheng
Department of Urology, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin (300211), China
Abstract:
Objective To clarify the therapeutic role of icariside Ⅱ(ICA Ⅱ) derivative YS10 in erectile dysfunction, as well as to investigate the possible molecular mechanisms. Methods 40 SD male rats were randomly divided into 4 groups: sham group, BCNI group, ICAⅡ group and YS10 group, 10 rats in each group. ICAⅡ and YS10 groups were given 2.5 mg/(kg·d) of the corresponding solvent by gavage, and the rest of the groups were given equal doses of saline. ICP, MAP and ICPmax/MAP values were measured after 4 weeks to evaluate the erectile function of rats respectively. Masson, HE and transmission electron microscopy experiments were performed to identify the morphological changes of endothelial cells. Western blotting and ELISA were performed to detect relevant endothelial indexes. Finally, the PI3K/AKT pathway was verified. Results Compared with BCNI group, ICAⅡ group and YS10 group showed statistical difference in ICPmax/MAP (P <0.001). Masson and HE showed that smooth muscle atrophy, collagen deposition, endothelial and neurological dysfunction were reduced. Transmission electron microscopy showed that the microstructure of ICAⅡ group and YS10 group was significantly improved. Western blotting showed that the expression levels of α-SMA and Calponin1 in the endothelium of ICAⅡ group and YS10 group were significantly higher than that in the BCNI group (P <0.05); ELISA showed that the eNOS and nNOS level of ICAⅡ and YS10 groups were higher than BCNI group. The expression of PI3K and p-AKT/AKT was significantly increased in ICAⅡ and YS10 groups (P <0.05).Conclusion ICAⅡ and YS10 can repair the disproportionate smooth muscle/collagen fibre ratio of penile corpus cavernosum and improve the pathological structure, YS10 may be superior to ICAⅡ in improving penile erectile function, and the PI3K/AKT signalling pathway may play an important role in restoring the penile erectile function by YS10 and ICAⅡ.
