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Effects of icariin on the erectile function and expression of nitrogen oxide synthase isoforms in corpus cavernosum of arterigenic erectile dysfunction rat model

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Abstract

The study the effects of oral administered icariin on intracavernosal pressure (ICP) and on expression of the nitrogen oxide synthase (NOS) isoforms in corpus cavernosum (CC) of arteriogenic erectile dysfunction (A-ED) rat model. Forty adult male Wistar rats were randomly divided into 4 groups of 10 rats: shame operated group (group A) and three A-ED model groups (group B, C and D). The internal pudendal arteries were isolated and ligated with 7-O nylon thread at both the main trunk and the penile branches to establish the A-ED model. ICP were tested after the operation to make sure the successful model establishment. The groups A and B were treated with saline: and the groups C and D were treated with icariin (5 mg/kg/day and 10mg/kg/day respectively) orally for 30 days. Then the ICP was measured again. The tissues of corpus cavernosum were taken and RT-PCR was used to detect the mRNA expression of nNOS, iNOS and eNOS in CC, and Western-blot was used to detect the protein expression of these NOS isoforms. The ICP in the group B was significantly decreased compared to the group A (P < 0.01), but the ICP values in the groups C and D were both increased compared to those in the group B (both P < 0.01). The expressions of the mRNA and protein of nNOS, iNOS, and eNOS were all decreased in the group B, however, the mRNA and protein expressions of eNOS were increased a in the groups C and D. In the group C, iNOS also increased. The expression of nNOS showed no obvious changes in the group C and group D. Chronic oral treatment with Icariin increases the erectile function (ICP) and restores the eNOS expression in CC of A-ED rats. Icariin may have a long-term therapeutic effect on ischemia/hypoxia induced ED.

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... Such relaxation could be inhibited by NOS specific inhibitor, N ω -Nitro-L-arginine (L-NNA). We also observed that icariin increased intracavernosal pressure (ICP) significantly, which could be conversely inhibited by L-NNA, without any influence on the mean arterial pressure (MAP) in another model [9]. ...
... Icariin was purified from the extract of Epimedii herba by high-speed counter-current chromatography with a two-phase solvent system composed of n-hexane-n-buta nol-methanol-distilled water (1:4:2:6, v/v) as described previously [7,9]. The purity was higher than 98.6 %. ...
... iNOS and eNOS content in rat cavernosal tissue can also be upregulated by single reagent VEGF [5]. In our previous study, chronic oral treatment with Icariin increases the erectile function (ICP) and restores the eNOS expression in corpus cavernosum of arteriogenic erectile dysfunction rats [9]. ...
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To investigate the effect of icariin on erectile function and the expression of nitric oxide synthase (NOS) isoforms in castrated rats. Thirty-two adult male Wistar rats were randomly divided into one sham-operated group (A) and three castrated groups (B, C and D). One week after surgery, rats were treated with normal saline (groups A and B) or oral icariin (1 mg/[kg.day] for group C and 5 mg/[kg.day] for group D) for 4 weeks. One week after treatment, the erectile function of the rats was assessed by measuring intracavernosal pressure (ICP) during electrostimulation of the cavernosal nerve. The serum testosterone (ST) levels, the percent of smooth muscle (PSM) in trabecular tissue, and the expression of mRNA and proteins of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and phosphodiesterase V (PDE5) in corpus cavernosum (CC) were also evaluated. ICP, PSM, ST and the expression of nNOS, iNOS, eNOS and PDE5 were significantly decreased in group B compared with those in group A (P 0.01). However, ICP, PSM and the expression of nNOS and iNOS were increased in groups C and D compared with those in group B (P 0.05). Changes in ST and the expression of eNOS and PDE5 were not significant (P 0.05) in groups C and D compared with those in group B. Oral treatment with icariin ( 98.6 % purity) for 4 weeks potentially improves erectile function. This effect is correlated with an increase in PSM and the expression of certain NOS in the CC of castrated rats. These results suggest that icariin may have a therapeutic effect on erectile dysfunction.
... Gingko biloba has been shown to relax vascular smooth muscle and this mechanism of action is thought to contribute to an improvement in ED [29]. Icariin, the active ingredient from Epimedium sagitattum, improved the erectile function and expression of nitric oxide synthase in castrated rats [30,31]. ...
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Background: Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. Methods: 78 men aged 25-50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator's Global assessment and Subjects' opinion. Results: In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the treatment they received. Investigator's global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject's rating for tolerability of treatment was similar in both groups. Conclusions: VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. Trial registration: Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009.
... Consistent with these reports, we hypothesized that the high anti-apoptotic activities of these four flavonoids in the vascular endothelial cells treated by Ox-LDL may be associated with their powerful antioxidant capacity. Previous study has shown that flavonoids could increase the mRNA and protein expression of eNOS in rats [33]. Therefore, these four flavonoids may increase the expression to promote the growth of eNOS. ...
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In this study, we performed a phenotypic screening in human endothelial cells exposed to oxidized low density lipoprotein (an in vitro model of atherosclerotic endothelial dysfunction) to identify the effective compounds in Shixiao San. After investigating the suitability and reliability of the cell-based screening method using atorvastatin as the positive control drug, this method was applied in screening Shixiao San and its extracts. The treatment of n-butanol fraction on endothelial cells exhibited stronger healing effects against oxidized low density lipoprotein-induced insult when compared with other fractions. Cell viability, the level of nitric oxide, endothelial nitric oxide synthase and endothelin-1 were measured, respectively. The assays revealed n-butanol fraction significantly elevated the survival ratio of impaired cells in culture. In parallel, n-butanol fraction exhibited the highest inhibition of inflammation. The generation of prostaglandin-2 and adhesion molecule (soluble intercellular adhesion molecule-1) was obviously declined. Furthermore, n-butanol fraction suppressed the production of reactive oxygen species and malondialdehyde, and restored the activity of superoxide dismutase. Compounds identification of the n-butanol fraction was carried out by ultra high liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. The active ingredients including quercetin-3-O-(2G-α-l-rhamnosyl)-rutinoside, quercetin-3-O-neohesperidoside, isorhamnetin-3-O-neohesperidoside and isorhamnetin-3-O-rutinoside revealed the ability of anti-atherosclerosis after exposing on endothelial cells. The current work illustrated the pharmacology effect of Shixiao San and clearly indicated the major active components in Shixiao San. More importantly, the proposed cell-based screening method might be particularly suitable for fast evaluating the anti-atherosclerosis efficacy of Traditional Chinese Medicines and screening out the interesting ingredients of Traditional Chinese Medicines.
... Furthuremore, the testosterone mimetic properties of flavonoid glycosides especially icarrin, icariside II [42] and its enhancing effects on expression of endothelial nitric oxide synthase (eNOS) and nitric oxide production in human endothelial cell [43,44], increased the intracavernous pressure response in rat [45], while the high intravenous pressure response was abolished by inhibitors of nitric oxide synthase and guanylate cyclase [45], which reduced the caspase-3 expression and cellular apoptosis in response of hydrogen peroxide [43,44]. Flavonoid glycosides had ameliorating effects on erectile functions of castration, arteriogenic and cavernous nerve injury and the neuronal nitric oxide synthase content (nNOS) of neuron penile in rats [46,47]. Icariin increased the nNOS and calponin expression in penile tissues and smooth muscles. ...
Article
Epimedium sp. is famous for its potency as sexual enhancer and five species of Epimedium brevicornum, E. sagittatum, E. pubescens, E. koreanum, and E. wushanense were recorded as Epimedium Herba (Yin Yang Huo) in Chinese Pharmacopeia. The aim of this study was to evaluate the potential efficacy of E. brevicornum as remedy for sexual dysfunction and infertility. For preparing this manuscript, we searched in all accessible resources (PubMed, Science direct, Wiley, Springer, and Google), books, thesis, and pharmacopeia. There are different traditional prescriptions from E. brevicornum, which are used for treatment of impotence and sexual disorders. Although, there is no clinical study on efficacy and safety of E. brevicornum on sexual functions, but animal and experimental analysis exhibited that E. brevicornum is and estrogenic plant and its flavonoid glycosides are inhibitors of phosphodiesterase 5 (PDE 5) and improved the erectile dysfunction, libido, impotence, sperm quality and fertility . Due to the lack of clinical study on efficacy of E. brevicornum, designing the human clinical study on safety and efficacy of standard E. brevicornum can be the subject of future studies.
... Icariin is the active component of traditional Chinese herb epimedium that helps in male impotence, erectile function by various mechanisms that preserve the expression of NOS and inhibit PDE5 activity which increases the cGMP levels in hypertensive rats spontaneously [63] . It is also helpful in streptozotocin-induced diabetic rats that improve erectile function by down-regulating the TGFβ1/Smad2 signaling pathway in oral icariin treatment. ...
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Erectile dysfunction (ED) or male impotence is described as an inability to maintain penile erection primarily endothelial and neuronal dysfunction which is partly characterized by decreased production of nitric oxide (NO). Male impotence can be caused by androgen deficiency in aging men, atherosclerosis, diabetes mellitus, spinal cord injury, high level of cholesterol, hypertension, prostate surgery, prostate and heart disease, penis anatomical deformity, social and psychological conditions as unhappy marital relationship, depression, and stress. Aphrodisiac is a drink or food that arouse sexuality. It can be categorized into three groups according to their action mode as follows: increase sexual pleasure substances, increase libido substances (arousal, sexual desire), and increase sexual potency (erection effectiveness). Various extracts of medicinal plants and orally active drugs such as vardenafil, sildenafil, and tadalafil are used to increase arterial blood flow for treating (ED) in southwest Asia. Hence, this paper review focuses on medicinal plants used as aphrodisiacs for scientific validation and management of erectile dysfunction (ED).
... В других эксперимента х икариин ингибировал активность фосфодиэстеразы пятого типа и повышал уровень циклического гуанозинмонофосфата в гладкомышечных клетках пещеристых тел [17]. При моделировании ЭД путем перевязки внутренней половой артерии при применении икариина (5 и 10 мг/кг/сут) зарегистрировано повышение давления в пещеристых телах с одновременным восстановлением экспрессии NO [18]. В последующих исследованиях установлен дозозависимый эффект и концентрации, при которых икариин и другие флавоноиды ингибируют ферменты, ответственные за развитие ЭД: фосфодиэстеразу пятого типа, аргиназу и ангиотензинпревращающий фермент [15,[19][20][21][22]. Перс пек т и вы фи то тера п и и у больных ЭД изучались нами на примере биологически активной добавки Виалиссил [23]. ...
... В другом исследовании икариин ингибировал Таблица 3. Содержание половых гормонов в сыворотке крови у пациентов с доброкачественной гиперплазией предстательной железы и эректильной дисфункцией до и после лечения О р и г и н а л ь н а я с т а т ь я 51 активность фосфодиэстеразы 5-го типа (ФДЭ-5) и повышал уровень циклического гуанозинмонофосфата в гладкомышечных клетках пещеристых тел [31]. У крыс с ЭД, смоделированной путем перевязки внутренней половой артерии, после перорального применения икариина в дозах 5 и 10 мг/кг/сут в течение 30 дней наблюдалось улучшение эректильной функции -повышение давления в пещеристых телах и восстановление экспрессии NO [32]. Несомненно, полученные экспериментальные данные нельзя экстраполировать на человеческий организм, но результаты проведенных экспериментов показывают механизм действия растительного сырья. ...
Article
The study objective is to evaluate clinical effectiveness of a phytopharmaceutical Vialissil® for treatment of patients with benign prostatic hyperplasia (BPH) and erectile dysfunction. Materials and methods . At the multi-specialty clinic “Family Doctor” (Saint Petersburg) 34 patients aged from 55 to 67 years (mean age 59.6 + 0.7 years) with BPH and concomitant erectile dysfunction without the need for surgical intervention were examined. All patients received previously prescribed symptomatic therapy for BPH and erectile dysfunction (a-adrenoblockers and phosphodiesterase type 5 inhibitors on demand). The treatment group included 18 patients who additionally received Vialissil® as capsules once a day for 30 days. The remaining 16 patients were the control group. Results. After treatment, intensity of general symptoms decreased more in the treatment group than in the control group (by 10 and 4 points, respectively). After the course of therapy, erectile function improved in both groups but only in the treatment group these dynamics were statistically significant. An increase in testosterone level was statistically significant only after combination therapy with Vialissil® (by 16.5 %), and blood level of biologically accessible (active) testosterone increased twofold. Conclusion. Combination therapy for BPH and erectile dysfunction including administration of the Vialissil® phytopharmaceutical more effectively decreases disease intensity compared to standard therapy.
... In this study, the HPLC fingerprint of the EDP1-001(1) extract using flavone as a marker was performed for quality control, with the flavone content of 58 g/mg extract ( Figure 2). Both flavonoids and phenolic compounds have been reported to be related to NO production stimulation [27][28][29], with the possible mechanism of increasing mRNA and protein expression of endothelial NO synthase (eNOS) in rats [34]. NO might be stimulated and released directly in the endothelial cells by activating the eNOS. ...
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Seven plants in the top rank were selected from the “MANOSROI III” database using the two Thai keywords which meant impotence and sexual tonic. Boesenbergia rotunda (L.) Mansf. extract [EDP1-001(1)] gave the highest PDE inhibition activity of 4.36-fold sildenafil, a standard anti-impotence drug. Plumbago indica Linn. extract [EDP2-001(1)] exhibited the highest NO release stimulation activity of 666.85% which was 1.50-fold acetylcholine, a standard drug. Most selected plant extracts were nontoxic to EA.hy926 cells at 1.0 mg/mL. EDP1-001(1) exhibited the LD 50 value of acute oral toxicity in male ICR mice of over 5,000 mg/kg body weight. EDP1-001(1) also indicated the improvement of sexual behaviors in the paroxetine-induced sexual dysfunction male mice with the evaluation of number of courtships (NC), mount frequency (MF), intromission frequency (IF), and ejaculatory frequency (EF) at 87.67±6.17 , 121.00±23.50 , 36.00±3.21 , and 13.67±2.96 which were 2.63-, 1.27-, 0.53-, and 0.62-fold sildenafil-treated mice at day 14 of the treatments, respectively. The present study has not only confirmed the traditional use of Thai plants for the treatment of ED but also indicated the potential and application of the “MANOSROI III” database for Thai plant selection to be developed as ED food supplements.
... Xiao et al. investigated the safety and efficacy of ICA in persons with a psychiatric illness at a dose up to 300 mg/day for eight weeks and observed no significant no side-effects [63]. Although no major side effects have yet been reported, ICA is considered about 1/80th as powerful of a PDE5 inhibitor, which may theoretically has a stimulatory effect and may affect vision, hearing and the stomach in very high doses [64][65][66]. More long-term toxicity studies about ICA are needed. ...
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To investigate whether the systematic administration of icariin (ICA) promotes tendon-bone healing after rotator cuff reconstruction in vivo, a total of 64 male Sprague Dawley rats were used in a rotator cuff injury model and underwent rotator cuff reconstruction (bone tunnel suture fixation). Rats from the ICA group (n = 32) were gavage-fed daily with ICA at 0.125 mg/g, while rats in the control group (n = 32) received saline only. Micro-computed tomography, biomechanical tests, serum ELISA (calcium; Ca, alkaline phosphatase; AP, osteocalcin; OCN) and histological examinations (Safranin O and Fast Green staining, type I, II and III collagen (Col1, Col2, and Col3), CD31, and vascular endothelial growth factor (VEGF)) were analyzed two and four weeks after surgery. In the ICA group, the serum levels of AP and OCN were higher than in the control group. More Col1-, Col2-, CD31-, and VEGF-positive cells, together with a greater degree of osteogenesis, were detected in the ICA group compared with the control group. During mechanical testing, the ICA group showed a significantly higher ultimate failure load than the control group at both two and four weeks. Our results indicate that the systematic administration of ICA could promote angiogenesis and tendon-bone healing after rotator cuff reconstruction, with superior mechanical strength compared with the controls. Treatment for rotator cuff injury using systematically-administered ICA could be a promising strategy.
... 7 Furthermore, icariin has successfully ameliorated both castration-related and arteriogenic impairment of erectile function and has reduced penile neuron NOS concentration in a rodent model. 8 However, the effect of icariin in inhibiting PDE5 is much weaker. 9 Therefore, chemical modifications of the native structure of icariin have been extensively conducted to achieve high PDE5 inhibitory activity and multiple effects in the NO-cGMP pathway. ...
Article
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.Asian Journal of Andrology advance online publication, 25 June 2012; doi:10.1038/aja.2011.175.
... 11 Lowinvasiveness surgery is beneficial to maintaining the physiological stability of the animal over a long period while monitoring possible drug reactions. 12,13 Furthermore, some urological researches are designed to determine the role of testosterone and nitric oxide in the maintenance of the erectile response in rats. 9,14 Such investigations require an index that reflects the erectile state. ...
Article
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Knowledge of the time course of penile erection is very important to understanding erection physiology. The changes in the intracavernosal pressure (ICP) and the different phases of an erection are pivotal to the ability to produce and maintain a rigid penile erection. This study investigated an objective and low-invasiveness method for identifying different erection phases based on an innovative ICP analysis technique. Blood infuses into the corpora cavernosa and causes the ICP to increase. The ICP usually exhibits tiny oscillations at the frequency of the heartbeat when it increases from diastole to systole. The characteristic oscillation amplitudes corresponding to the period when the full and rigid erection phases begin can be extracted by power spectral density analysis. The reliability and accuracy of the proposed method was verified by the Bland-Altman graphs indicating a good agreement with the existing method that compares the ICP with the arterial pressure. Moreover, all of the intraclass correlation coefficient values were close to 1.00, with the lower limit of the 95% confidence interval exceeding 0.75. The described novel objective and low-invasiveness method can therefore be used for identifying the full and rigid erection phases of the penis in urological investigations during different erection phases.
... ICA has also been demonstrated to increase the intracavernous pressure (ICP) response triggered by cavernous nerve stimulation in rats; these effects were abolished by inhibitors of nitric oxide synthase and guanylate cyclase [7]. Furthermore, ICA has been used successfully to ameliorate both castration-related and arteriogenic impairment of erectile function and decline in penile neuron nNOS content in a rodent model [8,9]. To our knowledge, the utility of icariin for potentiation of erection in an animal model of radical pelvic surgery has not been explored. ...
Article
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. 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. 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. 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. 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. ICA may have neurotrophic effects in addition to known phosphodiesterase type 5 inhibiting effects.
... The active constituents have been found to be flavonoid glycosides, especially Icariin which is the major pharmacologically active constituent (Wang and Huang, 2000;Shen et al., 2007). Icariin (5-hydroxy-4′-methoxyl-8-prenylflavone-3-O-α-L-rhamnopyranoside-7-O-β-Dglucopyranoside) has been found to possess effective aphrodisiac (Qiao et al., 2002;Xin et al., 2003;Tian et al., 2004), immunomodulatory (Liang et al., 1997), hepatoprotective (Lee et al., 1995), cardio-protective (Zhang et al., 2000), vasodilatory (Guan et al., 1996), anti-depressant (Pan et al., 2005), anti-osteoporotic (Meng et al., 2005), antioxidant and anti-apoptotic activities (Wang and Huang, 2005). Because of its wellestablished medicinal properties, Icariin is the quality control standard in many Traditional Chinese Medicine at present (Wang and Lou, 2004). ...
Article
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Epimedium L. is well known medicinal genus of Chinese pharmacopoeia. Various species are ethno-botanically used against diseases of eye and kidney, impotence, asthma, arthritis and hypertension; besides being used as analeptic, expectorant, antibacterial, hypoglycemic, vasodilator and refrigerant. Recent studies have attributed most of these medicinal properties to its flavonoid glycosides, especially Icariin which is the major pharmacologically active constituent. Icariin has been found to possess effective aphrodisiac, antioxidant, immunomodulatory, hepatoprotective, cardioprotective, vasodilatory, antidepressant and anti-osteoporosis activities. Icariside-II, another active constituent, has cytotoxic and cytostatic effects on 6 cancer cell-lines, and immunosuppressive effects on allograft rejection. In this present study, Epimedium elatum Morr. and Decne., the only species of this genus growing in Indian subcontinent, has been investigated for its medicinal value by determining the content of pharmacologically active constituents, Icariin and Icariside-II, by HPLC method. HPLC analysis of alcohol extract of its shade dried parts was performed with reverse phase C-18 column. The mobile phase for Icariin was acetonitrile-water in gradient mode; while for Icariside-II, it was methanol-water. The effluent was monitored at 270nm. The results have revealed an appreciable content of Icariin and Icariside-II in its aerial and underground parts; the content being higher in populations growing at higher altitudes. The substantial presence of pharmacologically active constituents, Icariin and Icariside-II, in this species of Epimedium, signifies its value as a medicinal plant.
Article
The aim of this study was to explore the effects and mechanisms of Icarisid II (ICA-II) on enhancing the cellular cGMP in rat corpus cavernosum tissue (RCCT). Diabetes mellitus Wistar rats were induced by streptozotocin, and diabetic ED rats were selected for the RCCT culture by apomorphine. ICA-II was extracted and purified from Icariin (ICA) by enzymatic method. The RCCT was treated with ICA-II, ICA and Sildenafil at different concentrations. cGMP and nitric oxide synthase (NOS) activities were checked respectively by enzyme immunoassay. Meanwhile, nNOS, iNOS and eNOS in RCCT were checked by western blot. ICA-II evaluated the intracellular cGMP to 8.01 ± 1.02 pmol mg(-1) min(-1), which is much weaker than that from Sildenafil (12.4 ± 1.16 pmol mg(-1) min(-1)) (P < 0.05). There is no significant difference between ICA-II and ICA. With the treatment of 10 μm ICA-II for 24 and 48 h, nNOS expression was significantly increased in RCCT (P < 0.05), while the eNOS expression level was very low without any change. Notably, ICA-II increased the intracellular NOS activity significantly in vitro in RCCT. Except the PDE5 inhibitory effect, ICA-II increases the intracellular cGMP through the enhancement of nNOS expression and NOS activity in RCCT in vitro. ICA-II implies a potential compound for neurogenic erectile dysfunction by NO-cGMP pathway.
Article
Epimedium (Berberidaceae), is a genus of about 52 species in the family Berberidaceae, which also known as Rowdy Lamb Herb, Xianlinpi, Barrenwort, Bishop's Hat, Fairy Wings, Horny Goat Weed, and Yangheye or Yin Yang Huo (Chinese: ). Many plants have been proven to possess efficacy on sexual dysfunction and osteoporosis in traditional Chinese medicine (TCM). The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of Epimedium species. More than 260 compounds have been isolated; among them prenyl-flavonoids are the major constituents and also important chemotaxonomic markers. Modern pharmacology studies and clinical practice demonstrated that Epimedium and its active compounds possess wide pharmacological actions, especially in strengthening yang, hormone regulation, anti-osteoporosis, immunological function modulation, anti-oxidation and anti-tumor, anti-aging, anti-atherosclerosis and anti-depressant activities. Currently, effective monomeric compounds or active parts have been screened for pharmacological activity from Epimedium in vivo and in vitro.
Article
Objectives To investigate the effect of icariin on endothelial microparticles (EMP), endothelial progenitor cells (EPC), platelets, and erectile function in spontaneously hypertensive rats (SHR). Materials and Methods Twelve 8-week-old healthy male Wistar-Kyoto(WKY) rats and 12 SHR were randomly divided into four following groups: WKY control group (normal saline 1ml/d given by gavage), WKY+icariin group (icariin 10mg/kg•d dissolved in 1ml normal saline and given by gavage), SHR control group (normal saline 1ml/d given by gavage), and SHR+icariin group (icariin 10mg/kg•d dissolved in 1ml normal saline and given by gavage). Four weeks later, the maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), endothelial microparticles (EMP), endothelial progenitor cells (EPC), and vitronectin receptor (αVβ3) were measured in each group. Results Under 3V/5V electrical stimulation, the ICPmax/MAP in the SHR+icariin group (0.23 ± 0.03, 0.38 ± 0.02) was significantly higher compared to the SHR control group (0.12 ± 0.02, 0.20 ± 0.02)(P<0.05). PLT, MPV, and PDW in the SHR+icariin group (1103.67 ± 107.70 10^9/L, 9.08 ± 0.50fl, 11.87 ± 0.45%) were significantly lower than those in the SHR control group (1298.00 ± 89.54 10^9/L, 9.72 ± 0.44fl, 13.03 ± 0.59%)(all P < 0.05). EMP, EPC, and αVβ3 in the SHR+icariin group (1.01 ± 0.28%, 1.53 ± 0.65%, 2.13 ± 0.53%) were significantly lower than those in the SHR control group (1.58 ± 0.19%, 2.71 ± 0.64%, 3.76 ± 0.52%)(all P < 0.05). Moreover, ICPmax/MAP was strongly negatively correlated with PDW and αVβ3 (r>0.7), and ICPmax/MAP was moderately negatively correlated with MPV, EMP, and EPC (0.5<r<0.7). Conclusion Icariin may improve erectile function in SHR by reducing the content of EMP in blood and inhibiting the activation of the platelets. EMP, EPC, and platelet activation-related (MPV, PDW, and αVβ3) can be used as indicators for icariin to improve erectile function in SHR. This article is protected by copyright. All rights reserved
Article
Cellular movement is mainly orchestrated by actin-dependent cytoskeleton in which Rho GTPase Rac1 or vasodilator-stimulated phosphoprotein (VASP) closely collaborates. In the present in vitro study, we investigated the inhibitory effect and underlying molecular mechanism of icariin, a pure extract of the traditional Chinese medicine Herba epimedii, on the invasive and migration properties of human gastric cancer cell line BGC-823. At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. Together with icariin, the selected siRNA targeting Rac1 or VASP reinforced these inhibitory effects. Rac1-siRNA-dependent down-regulation of Rac1 led to a large drop in VASP expression, whereas VASP-siRNA led to a slight fall in Rac1 expression, implying that the amount of Rac1 may influence VASP expression level. Moreover, transfection with Rac1 plasmids pcDNA3-EGFP-Rac1-Q61L led to the enhancement in expression level of both Rac1 and VASP. These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug.
Article
The search for a remedy or a prescription that can enhance sexual function and/or treat male erectile dysfunction has been an obsession throughout known history. Whether it was an Eastern civilization or a Western one, religious or atheist, man's aspiration for a better or best "manhood" has been a history-time goal. This review will discuss the current research done on the most popular natural aphrodisiacs and examine the weight of evidence to support or discourage the use of any of these substances to enhance sexual desire and/or function. Review of the current evidence on the use of natural substances as aphrodisiacs. Efficacy of natural aphrodisiacs in enhancing sexual function in men and women. There is little evidence from literature to recommend the usage of natural aphrodisiacs for the enhancement of sexual desire and/or performance. Data on yohimbine's efficacy does not support the wide use of the drug, which has only mild effects in the treatment of psychogenic ED. Although there's a positive trend towards recommending ginseng as an effective aphrodisiac, however, more in depth studies involving large number of subjects and its mechanism of action are needed before definite conclusions could be reached. Data on the use of natural aphrodisiacs in women is limited. The current body of objective evidence does not support the use of any natural aphrodisiac as an effective treatment for male or female sexual dysfunctions. Potent men and men with ED will continue the search for natural aphrodisiacs despite the current disappointing data on their effectiveness. Care should be taken regarding the fraud addition of sildenafil analogues to natural aphrodisiacs.
Article
To investigate effects of icariin on cardiac gene expression and the modulation of nitric oxide (NO) signal transduction during the differentiation of embryonic stem (ES) cells into cardiomyocytes in vitro. The expression levels of cardiac developmental-dependent genes were measured using reverse transcription-polymerase chain reaction (RT-PCR). The chronotropic responses of cardiomyocytes to b-adrenoceptor stimulation were determined. The levels of cAMP and cGMP in ES cells were measured using radioimmunoassay. Endogenous NO levels were measured by using the Griess reaction. Aminoguanidine (AG) was used to confirm the influence of icariin on the endogenous NO signal pathway. Icariin significantly elevated mRNA levels of cardiac transcription factors GATA4 and Nkx2.5, and cardiac-specific alpha-MHC, MLC-2v and beta-AR genes in a concentration- and time-dependent manner (P<0.05). Cardiomyocytes derived from embryoid body (EB) treated with icariin were more sensitive to isoprenaline (P<0.01). Treatment of ES cells with icariin resulted in a continued elevation in the cAMP/cGMP ratio before a shift to the cardiomyocyte phenotype (P<0.05). AG decreased the NO level, and delayed and decreased the incidence of contracting EB to only approximately 35% on d 5+11, an effect that could be rescued by icariin. When cells were cocultured with icariin and AG, the percentage of beating EB reached a peak level of 73% on d 5+11 (P<0.05). The inducible effects of icariin were partly related to increase in the expression of cardiac developmental-dependent genes, and elevation of the cAMP/cGMP ratio in ES cells, as well as upregulation of endogenous NO generation during the early stages of cardiac development.
Article
Icariin is a flavonoid isolated from Epimedium and is considered to be the major pharmacological active component of Epimedii Herba. In the present investigation, we studied and confirmed the protective activity of icariin on H2O2-induced injury in human umbilical vein endothelial cell line: ECV-304. Eighteen-hour treatment with 750 micromol l(-1) H2O2 significantly decreased the viability of ECV-304 cells, which was accompanied with apparent apoptotic features, including distinct cell morphological alteration and the increase of caspase-3 expression. In addition, it is observed that H2O2 increased the amounts of malondialdenhyde (MDA) and the dehydrogenase (LDH), and decreased the content of nitric oxide (NO) in ECV-304 cells. However, pretreatment with 0.1-50 micromol l(-1) icariin resulted in a significant recovery from H2O2-induced cell apoptosis. Also, it decreased other H2O2-induced damage in a concentration-dependent manner. Furthermore, pretreatment with icariin decreased the expression of caspase-3, which was known to be involved as a key role executor in H2O2-induced cell apoptosis. The endothelial cells apoptosis were detected by acridine orange/ethidium bromide (AO/EB) dual staining as well as flow cytometry, and the expression of pro-apoptotic factor caspase-3 were detected by immunocytochemical method. Taken together, these data suggest that protective effects of icariin against oxidative injuries of ECV-304 cells may be achieved via decreasing of caspase expression.
Article
Oxidative stress is implicated in male infertility and significantly higher reactive oxygen species are detected in 25% of infertile males. Although different agents of various alternative medicines, including traditional Chinese medicine, have been tried with varying success, evidence remains limited on whether and how much herbs or supplements might help increase the anti-oxidant ability of the sperm. This study examined the anti-oxidative effects of icariin, a flavonoid isolated from Herba Epimedii, on the human sperm. We prepared the FeSO4/H2O2-damaged human sperms, which were co-cultured with icariin in vitro, and then observed the changes of the sperm by employing Raman micro-spectroscopy. The results showed that Raman mapping with a 514 nm excitation laser allowed clear differentiation of the nucleus, neck, and, in particular, the mitochondria-rich middle piece of a human sperm cell. The effect of icariin on different organelles of the sperm was quantified by localized spectral Raman signatures obtained within milli-seconds, and icariin could keep the “Raman fingerprint” of the human sperm the same as the control groups, suggesting that icariin could protect the human sperm from being damaged by FeSO4/H2O2. Icariin may serve as a tonifying and replenishing agent of herbal origin for enhancing reproductive functions.
Article
The nitric-oxide (NO)-cyclic-guanosine-monophosphate (cGMP) pathway plays a key role in penile erection. Erectile dysfunction (ED) is a complication in male diabetic patients that impacts their quality of 1ife. Recently, Yidiyin, a Chinese herbal decoction, is used to treat diabetic ED, but convincing evidence is lacking, and the potential mechanisms remain uncertain. In the study, diabetic ED patients had low scores on international index of erectile function-5 (IIEF-5), and administration of Yidiyin and hypoglycemic drugs for 16 weeks ameliorated patients' scores on IIEF-5 more than the hypoglycemic drug alone. Moreover, streptozotocin-induced diabetes severely impaired rats' erectile function and the activity of the NO-cGMP pathway in the corpora cavernosum, and treatment with Yidiyin for 4 weeks obviously increased the rats' erectile function, remarkably enhanced the activity of nitric oxide synthase (NOS), and elevated the contents of NO and cGMP. Our findings indicate that Yidiyin improves diabetic ED probably by enhancing the NO-cGMP pathway.
Article
Polyphenols are a broad class of compounds. Some are ingested in substantial quantities from nutritional sources, more are produced by medicinal plants, and some of them are taken as drugs. It is becoming clear, that a single polyphenol is impacting several cellular pathways. Thus, a network approach is becoming feasible, describing the interaction of a single polyphenol with cellular networks. Here we have selected icariin to draw a prototypic network of icariin activities. Icariin appears to be a promising drug to treat major age-related diseases, like neurodegeneration, memory and depressive disorders, chronic inflammation, diabetes, and osteoporosis. It interacts with several relevant pathways, like PDE, TGF-ß, MAPK, PPAR, NOS, IGF, Sirtuin, and others. Such networks will be useful to future comparative studies of complex effects of polyphenols.
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Introduction: There has been a long history of man’s fascination with better and stronger sex drive and performance across different cultures. Several literature texts from the Hindu, Egyptian, Chinese and Roman civilizations document the human endless search for substances that can enhance sexual experiences and/or treat erectile dysfunction. Aim: This review will discuss the current research done on the most popular plant aphrodisiacs and provide evidence to support or discourage the use of any of them to enhance sexual desire and/or function in men. Methods: We review the current evidence on the use of natural substances as aphrodisiacs. Results: We found very little evidence to support the use of plant aphrodisiacs in the treatment of male sexual dysfunction. The vast majority of studies were conducted on animals with very few clinical studies. Available data suggest a beneficial effect of ginseng as a pro-sexual supplement and not an independent treatment for male sexual dysfunction. Conclusions: Trans-culturally, many herbal therapies show some potential benefits in improving men’s sexual function; however, adequate studies on the specific benefits and health risks associated with their use are needed. We strongly recommend the design and execution of well-controlled clinical studies to determine the efficacy and safety of plant aphrodisiacs.
Chapter
Several medicinal plants are traditionally used in different regions of Africa for the treatment of male infertility, sexual asthenia, erectile dysfunction, and impotency or used as an aphrodisiac. Scientific studies, mostly conducted in vitro or in animals, have proven the acclaimed traditional use of these plants to enhance sexual activities or sperm concentration, motility, and viability. Some of the mechanisms of actions associated with these plants include increased level of testosterone and the relaxation of the smooth cavernosal muscles. However, some plants were also shown to have detrimental effects on the male reproductive system. This may be due to the varying modes of plant extraction, duration of treatment, experimental design, dosage used, quality of the plant, or toxic effects. There is a need to standardize the protocols as well as to better understand the mechanism of actions of the respective plants. Further studies should be conducted using human subjects.
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In this chapter, you will be provided an overview of some of the most frequently used sports nutrition and physique-augmenting dietary supplements. For quick reference, the supplements are presented in alphabetical order using their Common, or “street” Name. The information is further presented in a revised and abbreviated monograph format. Each monograph details the dietary supplement by, 1) COMMON NAME, 2) OTHER NAMES (including, if applicable, abbreviations, primary plant source, and commercially licensed trade name), 3) COMMON USES (as pertaining to sports nutrition and physique augmentation), 4) REVIEW (of the relevant clinical data), and 5) DOSE (as has either been recommended in the literature or could confidently be determined to be safe and elicit an efficacious response).
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OBJECTIVE: To evaluate the effect of Yansheng granules on the sexual function and sexual organ development of castrated rats. METHODS: Castrated animal impotence model was employed to determine the erectile latency period and the weights of the preputial gland, seminal vesicle, prostate and levator ani muscle, so as to test the effect of Yansheng granules on the sexual function and sexual organ development of castrated rats. RESULTS: Yansheng granules at high dose could shorten the erectile latency period and extend the duration of erection of castrated rats. While in the middle and low dose groups the effect on the duration of erection was not significant. Yansheng granules showed no significant effect on sex gland in any dose group. CONCLUSION: Yansheng granules can shorten the erectile latency period, and extend the duration of erection of castrated rats, but have no significant effect on the gonad. The results of our experiments provide some theoretical and experimental evidence for the clinical application of this medicine.
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OBJECTIVE: To establish a HPLC-U V assay for the determination of icariside I in blood and tissue samples, and to study its pharmacokinetics and tissue distribution in rats. METHODS: Icariside I was analyzed on a Dikma C 18 column with the mobile phase consisting of methnol-0.2% phosphate acid (73:27) at 1.0 ml.·min-1 flow rate and with column temperature at 20°C. The wavelength of U V detector was set at 270 nm. A single dose of 10 mg·kg-1 icariside] was administrated intravascularly in rats. The icariside I concentrations in blood and tissues were assayed by HPLC-UV method. The pharmacokinetic parameters of icariside I were calculated by 3P97 program. RESULTS: The concentration-time curve of icariside I was fitted to a two-compartment model. Icariside I was remained in heart and muscle in some degree. CONCLUSION: The method was convenient, accurate and specific. It was suitable for the study on pharmacokinetis and tissue distribution of icariside I.
Article
• Clinical data supports the use of Korean ginseng for the treatment of erectile dysfunction and male libido problems • More research is required to confirm the efficacy of maca, tribulus and horny goat weed, however small trials and preclinical data lend support • Saw palmetto does not appear to improve sexual function • Men's sexual health problems should be viewed in the context of potential generalised endothelial dysfunction, and psychogenic factors should also be considered.
Article
Epimedium is a well known genus of Chinese pharmacopoeia, possessing various medicinal properties such as aphrodisiac, antioxidant, immunomodulatory, vasodilatory, hepatoprotective, cardioprotective, antidepressant, anticancerous and antiosteoporosis activities. The active principle has been found to be its flavonoid glycosides, especially Icariin and Icariside-II. In the present study, Epimedium elatum, the only species of this genus growing in Indian subcontinent and endemic to Kashmir Himalayas, has been studied for its active principle content at different habitats. The plants were collected from wild populations (W-I W-II &W-III) growing at three different sites of different altitudes and cultivated at low altitudes of Central Kashmir. After two years, the plants from wild populations as well as cultivated populations were collected, shade dried, grinded and prepared for HPLC analysis. The results showed that the content of active principles in leaves vary significantly between plants growing at different habitats. The Icariin and Icariside-II yield (per plant) of wild populations significantly increased with a decrease in altitude of habitat. Cultivated population growing at higher altitude had significantly more yield than all other populations, except the W-III. The content of active principles as a percentage of leaf dry mass increased with increase in altitude. However, the harvest index of wild populations showed a decreasing trend with increasing altitude. The content of active principles as a percentage of dry mass of whole plant was comparable in all the habitats, including the cultivated populations. The present study suggests that Epimedium plants cultivated at lower altitudes are equally or more productive in terms of Icariin and Icariside-II content than that of wild plants growing at higher altitudes.
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Traditional Chinese Medicine (TCM) has a long history in the treatment of andrological diseases. TCM has its own unique philosophy of diagnosing and treating andrological diseases, such as the Yin and Yang or Qi and Viscera theories. Six tonic herbs are listed and discussed in this chapter in terms of their traditional record in andrological disease management and pharmacological effects in andrology. This includes the protective effects on reproductive function, spermatogenesis, erectile dysfunction, antiprostate cancer, and on benign prostatic hyperplasia. The six TCM herbs are Herba Epimedii, Lycium barbarum, Herba Cistanches, Cuscutae Semen, Morinda officinalis Radix, Psoralea Fructus.
Article
Icariin, a flavonoid isolated from Epimedii herba, is considered to be the major therapeutical constituent of E. herba. The aim of this study was to investigate the possible protective effects and to clarify the mechanism of icariin on endothelial cells in vitro. Incubation of human umbilical vein endothelial cells (HUVEC) derived EA. hy926 cells with icariin(0.1, 1, 10 micromol l(-1)) from 6 h to 72 h, then the production of NO was measured to evaluate the protective effects of icariin. RT-PCR was employed to confirm the mRNA expression of endothelial nitric oxide synthase (eNOS). Western blotting was used to evaluate the protein expression of eNOS. NO production was enhanced in a time- and concentration-dependent manner (P<0.05), which was well matched with the expression of eNOS mRNA (up to 2.4-fold) and protein (up to 2.5-fold) after long-term incubation with icariin in endothelial cells (P<0.05). Moreover, activated NF-kappaB was increased in EA. hy926 cells incubated with icariin for 24 h, in association with an increase in the expression of eNOS gene. In addition to its long-term effects on eNOS expression, icariin also enhanced the production of bioactive NO in the short-term (after a 5 min incubation, P<0.05). In concert with other effects, the protective effects of icariin on endothelial cells may contribute to the cardiovascular protective effects.
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