Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO–cGMP pathway

Abstract

Erectile dysfunction (ED) is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid II. This study investigates the effects of icarisid II on diabetic rats with ED and its potential mechanism via the assessment of advanced glycosylation end products (AGEs), autophagy, mTOR and the NO-cGMP pathway. Icarisid II was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid II group, rats were administered icarisid II intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure (ICP/MAP). AGE concentrations, nitric oxide synthase (NOS) activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 localisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid II increased ICP/MAP values, the smooth muscle cell (SMC) growth curve, S phase and SMC/collagen fibril (SMC/CF) proportions and decreased Beclin 1 (P,0.05). Icarisid II significantly increased the proliferative index and p-p70S6K(Thr389) levels and decreased the numbers of autophagosomes and the levels of LC3-II (P,0.01). Icarisid II decreased AGE concentrations and increased cGMP concentration, NOS activity (P,0.05) and cNOS levels (P,0.01) in the diabetic ED group. Therefore, Icarisid II constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.

Chronic treatment with taurine ameliorates diabetes‐induced dysfunction of nitric oxide‐mediated neurogenic and endothelium‐dependent corpus cavernosum relaxation in rats

“…The present study showed that induction of diabetes with STZ resulted in a decline in erectile function, as indicated by a decrease in both endothelium‐dependent and neurogenic corpus cavernosum relaxation of diabetic rats. This result confirmed previous findings indicating that diabetes was able to induce ED in experimental and clinical studies . The diminished ACh‐induced endothelium‐dependent relaxation can be explained by several mechanisms.…”

Effect of rutin on diabetic-induced erectile dysfunction: Possible involvement of testicular biomarkers in male rats

“…With antioxidants being so abundant in many plants, they could have an important influence on human health. Flavonoids are known to improve erectile function by their antioxidant and anti‐inflammatory properties (Yang, Gao, Wang, Su, & Xing, ; Zhang et al., ). In present study, treatment with RT to diabetic rats improved the cGMP levels in penile tissue as compared to untreated diabetic rats, and this may be justified by its pharmacological potentials.…”

Therapeutic Response of Epimedium gandiflorum’s Different Doses to Restore the Antioxidant Potential and Reproductive Hormones in Male Albino Rats

“…Due to aphrodisiac properties induction in Chinese goat, E. grandiflorum is commonly known as horny goat weed. Icariin, a flavonol glycoside as active ingredient of this plant induce the nitric oxide (NO) synthesis in penis, 2 cavernosal smooth muscle where NO acts as inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), 3 and boost the proliferation of smooth muscle, and reduce the formation of advanced glycation end product 4 and caricaturist endogenous androgens. 5 These beneficial effects of Epimedium species are due to the presence of various phytochemical constituents; and about over 260 including alkaloids, flavonoids, proteins, glycosides, bioactive peptides, waxes, amino acids, phyto-hormones are responsible for beneficiary activities, have been isolated.…”