A flavonoid derivative of icariside II (YS-10) improves erectile dysfunction in radiation-injured rats via oxidative stress pathway

We explored the preventive effect and mechanism of YS-10, a novel synthesized flavonoid derivative based on the structure of icariside II (ICA II), on a rat model of radiation-induced erectile-dysfunction (Ri-ED).Eighteen 10-week-old male Sprague-Dawley (SD) rats were randomly divided into 3 groups. Six rats were used as the control group (Control), and the remaining 12 were given a single X-ray irradiation of 20 Gy in the prostate and then randomly divided into the radiation injury group (Ri-ED group) and YS-10 treatment group (Ri-ED+YS-10, 2.5 mg/kg/day). After 4 weeks of drug administration and a 2-week drug washout period in the YS-10 treatment group, the erectile function of the animals was evaluated, and the tissues were collected for histopathological analysis and detection of oxidative stress indicators.After radiation injury, the ratio of maximum intracavernosal pressure (ICP) to mean arterial pressure (MAP), the number of neuronal nitric oxide synthase (n-NOS) positive nerve fibers in the penis cavernosa, endothelial cell content, and n-NOS and endothelial nitric oxide synthase (e-NOS) proteins in the Ri-ED group were significantly lower than those in control group. Compared with the control group, the Ri-ED group had lower superoxide dismutase (SOD) levels and higher malondialdehyde (MDA) levels. Compared with the Ri-ED group, the YS-10 group had a significant increase in the ratio of ICP/MAP in the corpus cavernosum (0.59±0.06 vs. 0.43±0.06, P<0.01), the number of n-NOS positive nerve fibers, and the content of endothelial cells. The protein content of n-NOS and e-NOS in the corpus cavernosum increased and could significantly reduce the level of MDA (2.67±0.27 vs. 3.25±0.21, P<0.05).As a novel ICA II derivative, YS-10 could significantly improve the erectile dysfunction and pathological damage in rats caused by radiation injury, and its mechanism may be related to the improvement of radiation-induced oxidative stress.