A novel flavonoid derivative of icariside II improves erectile dysfunction in a rat model of cavernous nerve injury

Abstract

Background: Icariside II (ICA II), an active flavonoid monomer, has been proven to restore post-prostatectomy erectile dysfunction in rats; however, the high cost of extraction from natural plants limits the application of ICA II.Objective: To investigate the therapeutic effect and possible mechanism of action of YS-10, a new flavonoid compound, which was designed and synthesized based on the structure of ICA II in a rat model in of cavernous nerve injury.Materials/methods: Eight of 32 adult male Sprague-Dawley rats were selected as the normal control (NC) group and received vehicle treatment. The remaining rats were subjected to bilateral cavernous nerve injury (BCNI) and randomized into three groups: BCNI group, BCNI + ICA II group (2.5 mg/kg/day), and BCNI + YS-10 group (2.5 mg/kg/day). The total procedure lasted for 21 days, followed by a washout period of 3 days. All animals were evaluated for erectile function, and tissues were harvested for histopathological analyses. Results:It was observed that in YS-10 group, the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP) and the area under the ICP/MAP curve were effectively enhanced. The maximum ICP/MAP increased by 30% in the YS-10 group (0.86 ± 0.085) compared with the BCNI group (0.66 ± 0.058), which is close to 82% of the NC group (1.05 ± 0.033). Histopathological changes demonstrated significant reduction of smooth muscle atrophy, collagen deposition, and endothelial and neural dysfunction after YS-10 treatment, which have no statistical differences compared with ICA II group. Additionally, high-protein expression levels of β-Catenin and cyclin D1 were observed in the treatment groups.Conclusion: YS-10, a novel synthesized flavonoid compound, could effectively improve erectile dysfunction in rats after BCNI by alleviating pathological impairments; this effect may associate with the upregulation of β-Catenin and cyclin D1 in Wnt signaling pathway.

Acetyl‐L‐carnitine improves erectile function in bilateral cavernous nerve injury rats via promoting cavernous nerve regeneration

“…Moreover, we stimulated the CN between the MPG and the nerve injury site during evaluating the erectile dysfunction to analyze both nerve damage and erectile tissue injury, which was also recommended by the consensus statement 32 . By the above methods, we identified that erectile function was significantly impaired in the BCNI group, which is similar to previous reports 33 . Furthermore, cavernosal denervation can dampen erectile function through mechanisms like increased collagen content, fibrosis, apoptosis, penile endothelial dysfunction, and oxidative stress injury 34 .…”

“…32 By the above methods, we identified that erectile function was significantly impaired in the BCNI group, which is similar to previous reports. 33 Furthermore, cavernosal denervation can dampen erectile function through mechanisms like increased collagen content, fibrosis, apoptosis, penile endothelial dysfunction, and oxidative stress injury. 34 Using Masson trichrome staining, we found that smooth muscle/collagen ratio and smooth muscle marker α-SMA were substantially down-regulated in BCNI rats, accompanied by increased the penile fibrosis indicators TGF-β, CTGF, and Smad 2/3, which confirmed the CN is of paramount importance for erectile function.…”

Deciphering the myth of icariin and synthetic derivatives in improving erectile function from a molecular biology perspective: a narrative review

“…ICAII restored nerve density and microstructure of pelvic floor ganglia in the penile corpus cavernosum of ED rats with diabetes-induced nerve damage, and in vitro ICAII resulted in longer synapses and more branching of ganglion tissue ( 42 ). In addition, YS-10, a new flavonoid based on the ICA II structure, treated rats with bilateral cavernous nerve injury (BCNI) and showed a significant reduction in smooth muscle atrophy, collagen deposition, endothelial and neurological dysfunction ( 43 ). In order to assess the efficacy and mechanisms of ICA treated BCNI rat.…”

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

“…Briefly, the rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital (30 mg/kg), and a single dose of 20 Gy (2 Gy/min) was delivered by a medical linear accelerator. After irradiation, the rats were randomly divided into 2 equal groups: Ri-ED group and YS-10 treatment group (Ri-ED+YS-10, 2.5 mg/kg/day) (14). Twenty-four hours after irradiation, the 3 groups were treated with a vehicle (Control and Ri-ED groups) and YS-10 (Ri-ED+YS-10 group, 2.5 mg/kg) dissolved in polyethylene glycol 400 (PEG400) via intragastric administration daily for 4 weeks, followed by a washout period of 2 weeks.…”

“…Recently, YS-10 has been reported to treat erectile dysfunction. Through animal experiments, it was shown that YS-10 had the effect of repairing the pathological damage of the corpus cavernosum and improving erectile function, and the efficacy was not lower than ICA II (14). However, the pharmacological mechanism of YS-10 is still unclear.…”