Erectogenic and Neurotrophic Effects of Icariin, a Purified Extract of Horny Goat Weed (Epimediumspp.) In Vitro and In Vivo

Abstract

Introduction Epimedium species (aka horny goat weed) have been utilized for the treatment of erectile dysfunction in Traditional Chinese Medicine for many years. Icariin (ICA) is the active moiety of Epimedium species. Aim To evaluate the penile hemodynamic and tissue effects of ICA in cavernous nerve injured rats. We also studied the in vitro effects of ICA on cultured pelvic ganglia. Methods Rats were subjected to cavernous nerve injury and subsequently treated for 4 weeks with daily gavage feedings of a placebo solution of normal saline and Dimethyl sulfoxide (DMSO) vs. ICA dissolved in DMSO at doses of 1, 5, and 10 mg/kg. A separate group underwent a single dose of ICA 10 mg/kg 2 hours prior to functional testing. Functional testing with cavernous nerve stimulation and real-time assessment of intracavernous pressure (ICP) was performed at 4 weeks. After functional testing, penile tissue was procured for immunohistochemistry and molecular studies. In separate experiments, pelvic ganglia were excised from healthy rats and cultured in the presence of ICA, sildenafil, or placebo culture media. Main Outcome Measure Ratio of ICP and area under the curve (AUC) to mean arterial pressure (MAP) during cavernous nerve stimulation of subject rodents. We also assayed tissue expression of neuronal nitric oxide synthase (nNOS), eNOS: endothelial nitric oxide synthase (eNOS), calponin, and apoptosis via immunohistochemistry and Western blot. Serum testosterone and luteinizing hormone (LH) were assayed using enzyme-linked immunosorbant assay (ELISA). Differential length of neurite outgrowth was assessed in cultured pelvic ganglia. Results Rats treated with low-dose ICA demonstrated significantly higher ICP/MAP and AUC/MAP ratios compared with control and single-dose ICA animals. Immunohistochemistry and Western blot were revealing of significantly greater positivity for nNOS and calponin in penile tissues of all rats treated with ICA. ICA led to significantly greater neurite length in cultured specimens of pelvic ganglia. Conclusion ICA may have neurotrophic effects in addition to known phosphodiesterase type 5 inhibiting effects.

Rise of Herbal and Traditional Medicine in Erectile Dysfunction Management

“…In another study by Yakubu et al [73], testes to body weight ratio in treated rats was found to be higher compared to control after 28 days of F. agrestis stem aqueous extract treatment (18,50, and 100 mg/kg), and the ratio remained unchanged after washout period of 10 days.…”

“…In the latest study, rats with cavernous nerve injury, treated with lowdose ICA also demonstrated significantly higher ICP/mean arterial pressure ratio. Immunohistochemistry and Western blot also showed significantly greater positivity for nNOS and calponin in penile tissues of all rats treated with ICA [18].…”

Evaluation and Treatment of Erectile Dysfunction in the Aging Male: A Mini-Review

“…Recently, it was discovered that this enhancement is due to an inhibitory effect of both PDE4 and PDE5 by icariin [45] . Icariin was able to prevent fibrotic alterations in the corpus cavernosum after denervation in rats when administered daily by oral gavage [46] . Nutritional supplements such as antioxidants may reduce erectile tissue damage by radical oxygen species [47] .…”

Nutraceuticals for Fertility and Erectile Health: A Brief Overview of What Works and What Is Worthless

“…The testosterone increases are statistically significant but arguably not clinically significant as of yet. Horny Goat Weed (Epimedium species) contains a compound(s) known as "icariin" that may have a PDE-5 like effect [232][233][234], but clinical research is needed because the majority of the impressive research was derived from basic science studies, but still it is also one clinicians should monitor. MACA (Lepidium meyenii) has some preliminary positive clinical data in fertility and ED, but needs more consistent research on standardization of active ingredients and efficacy, but is commonly used in other countries such as Peru [235,236].…”