• Journal of Physiology & Pathology in Korean Medicine
• /
• v.25 no.5
• /
• pp.863-869
• /
• 2011

The aim of the present study is to investigate whether an ethanol extract of Acorus gramineus Soland (EAG) augments penile erection in vitro and in vivo experiment. Preconstructed with phenylephrine (PE) in isolated endothelium-intact rabbit corpus cavernosum, EAG relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-argininemethylester (L-NAME), a nitricoxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3-${\alpha}$]-quinoxalin-1-one (ODQ), a soluble guanylylcyclase (sGC) inhibitor, respectively. EAG-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA), a nonselective $K^+$ channel blocker. EAG increased cGMP levels of the rabbit corpus cavernosum in a concentration-dependent manner without changes in cAMP levels. In addition, EAG caused increase of peak intracavernous pressure (ICP), ICP/MAP ratio and area under the carve (AUC) in SD rats. Taken together, these results suggest that EAG augments penile erection via NO-cGMP system and $K^+$ channels in corpus cavernosum.

• Natural Product Sciences
• /
• v.23 no.3
• /
• pp.169-174
• /
• 2017

The aim of this study was to investigate the effect and action mechanism of quercetin on penile corpus cavernosum smooth muscle (PCCSM). PCCSM precontracted with phenylephrine (Phe) was treated with four different concentrations of quercetin ($10^{-7}$, $10^{-6}$, $10^{-5}$ and $10^{-4}M$). PCCSM were preincubated with N-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) to block nitric oxide synthase and guanylate cyclase, respectively. The changes in PCCSM tension were recorded, and cyclic nucleotides in the perfusate were measured by radioimmunoassay. The interactions of quercetin with phosphodiesterase type 5 inhibitors (PDE5-Is) such as sildenafil, udenafil and mirodenafil, were also evaluated. PCCSM relaxation induced by quercetin occurred in a concentrationdependent manner. The application of quercetin to PCCSM pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Quercetin significantly increased cGMP in the perfusate. Furthermore, quercetin enhanced PDE5-Is-induced relaxation of PCCSM. Quercetin relaxed the PCCSM by activating the NO-cGMP signaling pathway, and it may be a therapeutic candidate or an alternative treatment for patients with erectile dysfunction who do not completely respond to PDE5-Is.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.27 no.5
• /
• pp.602-610
• /
• 2013

This study was aimed to evaluate the cavernosal relaxation effect of Crataegii fructus(CF) in the contracted rabbit penile corpus cavernosum by agonists.In order to study the effect of CF on the vasoconstriction of rabbit penile corpus cavernosum, isolated rabbit penile corpus cavernosum tissues were used for the experiment using organ baths containing Krebs solution.To investigate the cavernosal relaxation of CF, CF extract at $0.01{\sim}3.0mg/m{\ell}$ was added after penile corpus cavernosum were contracted by norepinephrine(NE) $1{\mu}M$. To analyze the mechanism of CF's vasorelaxation, CF extract infused into contracted penile tissues by NE after each treatment of indomethacin(IM), $N{\omega}$-nitro-L-arginine(L-NNA), methylene blue(MB), tetraethylammonium chloride(TEA).To study the effect of CF on influx of extracellular calcium chloride($Ca^{2+}$) in penile tissues, in $Ca^{2+}$-free krebs solution, $Ca^{2+}$ 1 mM infused into contracted penile tissues by NE after pretreatment of CF. Cytotoxic activity of CF on human umbilical vein endothelial cell(HUVEC) was measured by MTT assay, and nitric oxide(NO) prodution was measured by Griess reagent. CF relaxed cavernosal strip with endothelium contracted by NE, but in the strips without endothelium, CF-induced relaxation was significantly inhibited. The pretreatment of L-NNA, MB, TEA decreased significantly on the cavernosal relaxation than not-treatment of them. But the pretreatment of IM had no significant effect on the cavernosal relaxation. In $Ca^{2+}$-free krebs solution, when $Ca^{2+}$ infused into contracted penile tissues by NE, pretreatment of CF inhibit contraction induced by adding $Ca^{2+}$.NO production wasn't increased by treatment of CF on HUVEC. This findings showed that CF is effective for the relaxation of rabbit penile corpus cavernosum, and we suggest that CF relax rabbit corpus cavernosal smooth muscle through multiple action mechanisms that include increasing the release of nitric oxide from corporal sinusoidal endothelium, inhibition of $Ca^{2+}$ mobilization into cytosol from the extracellular fluid, and maybe a hyperpolarizing action.

• Mycobiology
• /
• v.48 no.2
• /
• pp.153-156
• /
• 2020

Calvatia nipponica, a puffball mushroom (Agaricaceae), is thought to be an aphrodisiac, as this mushroom is traditionally known to improve sexual function in males. As part of the systematic study to determine the bioactive secondary metabolites from C. nipponica responsible for aphrodisiac effects, chemical analysis of methanol (MeOH) extracts of the fruiting bodies of C. nipponica resulted in the isolation of two major compounds: N,N-dimethyl-anthranilic acid (1) and (7Z,10Z)-7,10-octadecadienoic acid methyl ester (2). Compounds 1 and 2 were evaluated for cumulative dose-dependent relaxation responses to precontracted penile corpus smooth muscle (PCCSM). Results show that compounds 1 and 2 exhibited a maximum relaxation effect of 20.33 ± 2.18% and 24.63 ± 3.60%, respectively. These findings indicate that compounds 1 and 2, major components of C. nipponica, could potentially be used to treat erectile dysfunction, functioning as natural aphrodisiacs.

• Journal of Ginseng Research
• /
• v.20 no.3
• /
• pp.339-343
• /
• 1996

The effect of ginseng on the reactivity of penile corpus cavernosal smooth muscle strips of rabbits was investigated to support the clinical application of ginseng for the treatment of erectile dysfunction. New Zealand white rabbits were randomly divided into two groups, normal diet group (n=9) and ginseng saponin diet group (n=5). Then, each group was fed normal diet and Korean red ginseng saponin diet (50 mg/kg/day) for 10 weeks. We measured concentration dependent relaxation of corporal smooth muscle to acetylcholine (10-8 M to 10-4M) in organ chamber. The degree of relaxation was expressed as percentage of maximal relaxation obtained by papaverine (10-4M). Dose dependent relaxation of corpus cavernosal smooth muscle to acetylcholine, at the concentration of 10-8 M to 10-4M by half log increment, was 4.06$\pm$0.00, 4.30$\pm$1.30, 5.32$\pm$0.68, 11.64$\pm$1.74, 16.24$\pm$1.61, 23.33$\pm$ 2.29, 26.45$\pm$2.25, 30.43$\pm$2.40 and 33.41 $\pm$2.48 (%), respectively in normal diet group and 9. 83$\pm$4.15, 20.60$\pm$4.62, 24.1815.12, 35.75$\pm$5.71, 43.35$\pm$6.11, 51.30$\pm$6.22, 56.33$\pm$6.22, 54.30$\pm$4.17 and 51.98$\pm$3.92 (Vc), respectively in ginseng group. These data suggest that ginseng enhances ondothelium-dependent acetylcholine-induced relaxation of penile corpus cal.ernosal smooth muscle in rabbits.

• Korean Journal of Clinical Pharmacy
• /
• v.21 no.1
• /
• pp.1-5
• /
• 2011

Purpose: 본 연구는 토끼의 음경해면체 조직에 대한 인진쑥의 에탄올 추출물과 그 성분 중의 하나인 scoparone의 효능을 평가하고자 하였다. Methods: 체중이 2.5-3.0 Kg의 New Zealand백색 가토를 사용하여 음경 전체를 골반골로부터 분리하여 요도를 제거한 후 백막을 보유한 음경해면체를 2 mL organ chamber 관류모형에 연결하고, $10^{-5}M$의 phenylephrine을 관류하여 음경해면체를 수축시킨 후 0.1, 0.5, 1, 2 mg/mL의 에탄올 추출물 또는 $10^{-7}$, $10^{-6}$, $10^{-5}$, $10^{-4}M$의 scoparone을 녹인 용액으로 관류시켜 음경의 장력 변화를 측정하였다. 기존의 발기부전 치료제로 사용되는 실데나필에 대한 인진쑥과의 상호작용을 검토하기 위하여$10^{-6}M$의 scoparone과 $10^{-8}M$의 실데나필을 병용 사용 시 음경해면체 조직에 대한 효과도 함께 검토하였다. Results: 인진쑥의 에탄올 추출물은 phenylephrine으로 전처리하여 수축시킨 음경해면체 평활근을 농도 의존적으로 효과적으로 이완시켰으며 scoparone도 음경해면체 조직에 대한 이완작용 또한 농도 의존적으로 강한 효과를 나타내었다. 실데나필로 전처리한 음경해면체 조직에 대한 scoparone의 효과는 scoparone만을 단독으로 관류시킨 조직에서의 효과보다 강하게 나타났으며 실데나필과 scoparone의 병용사용은 실데나필의 효능을 2배 이상 증가시켰다. Conclusions: Scoparone은 실데나필의 음경해면체평활근 작용을 증가시킴으로써 실데나필에 완전히 반응하지 않는 환자들의 발기부전 치료효과 향상에 유용할 것으로 전망된다.

• Nutrition Research and Practice
• /
• v.12 no.4
• /
• pp.291-297
• /
• 2018

BACKGROUND/OBJECTIVES: This study evaluated the effects and molecular mechanisms of the Schisandra chinensis fruit extract (SC) and its major compound gomisin A (GA), on the contractility of rabbit penile corpus cavernosum smooth muscle (PCCSM). MATERIALS/METHODS: PCCSM was exposed to SC or GA after appropriate pretreatment with nitric oxide synthase (NOS) blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker. Subsequently, we evaluated the cyclic nucleotide in the perfusate by radioimmunoassay, protein expression level of neuronal NOS (nNOS) and endothelial NOS (eNOS) by western blot, and the interaction of SC or GA with udenafil and rolipram. RESULTS: Both SC and GA induce PCCSM relaxations in a concentration-dependent manner. Pretreatment with NOS blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker result in significantly decreased relaxation. SC and GA also induce the levels of cyclic nucleotide in the perfusate in a concentration-dependent manner. Perfusion with GA also showed significantly higher levels of eNOS protein. Furthermore, the udenafil and rolipram induced relaxations of PCCSM were enhanced after exposure to SC and GA. Our results indicate that SC and GA induce the relaxation of PCCSM via the nitric oxide (NO)-cGMP and cAMP signaling pathways. CONCLUSIONS: The SC and GA are potential alternative treatments for men who want to consume natural products to ameliorate erectile function, or who do not respond to the commercially available medicines.

• Archives of Pharmacal Research
• /
• v.25 no.6
• /
• pp.873-878
• /
• 2002

OA-8159, a new Phosphodiesterase (PDE) 5 inhibitor, has exhibited potent erectogenic potential in a penile erection test in rats and anesthetized dogs. In this study, we investigated the mechanism of its erectogenic activity by measuring the activity of OA-8159 against a various PDE isozymes and assessing cGMP and cAMP formation in a rabbit corpus cavernosum in vitro. DA-8159 inhibited the PDE 5 activity in rabbit and human platelets, which the $IC_{50}$ was 5.84$\pm$1.70 nM and 8.25$\pm$2.90 nM, respectively. The $IC_{50}$ of DA-8159 on PDE 1, PDE2, PDE 3 and PDE 6 were 870$\pm$57.4 nM, $101\pm$5 $\mu$M, 52.0$\pm$3.53 $\mu$M and 53.3$\pm$2.47 nM, respectively. This suggests that DA-8159 is a potent, highly selective, competitive inhibitor of PDE 5-catalyzed cGMP hydrolysis. The rates of cGMP hydrolysis catalyzed by human platelets-derived PDE 5 as a function of the cGMP concentration (5~100 nM) and two-fixed DA-8159 concentration (11.3 and 18.8 nM) were investigated in order to characterize the mode of PDE 5 inhibition by DA-8159. DA-8159 increased the apparent 4K_{m}$ value for cGMP hydrolysis but had no effect on the apparent $V_{max}$, indicating a competitive mode of inhibition. DA-8159 increased the cGMP concentrations in the rabbit corpus cavernosum dose dependently. In the presence of sodium nitroprusside (SNP), DA-8159 significantly sti\mulated the accu\mulation of cGMP when compared to the control level. This indicated that the enhancement of a penile erection by DA-8159 involved the relaxation of the cavernosal smooth \muscle by NO-sti\mulated cGMP accu\mulation. In conclusion, DA-8159 is a selective inhibitor of PDE 5-catalyzed cGMP hydrolysis and the enhancement of a penile erection by DA-8159 is mediated by the relaxation of the cavernosal smooth \muscle by the NO-sti\mulated cGMP accu\mulation.

• Journal of Ginseng Research
• /
• v.40 no.4
• /
• pp.334-343
• /
• 2016

Background: Progressed tissue culture techniques have allowed us to easily obtain mass products of tissue-cultured mountain ginseng over 100 yr old (TCMG-100). We investigated the effects of TCMG-100 extract on erectile function using in vitro and in vivo studies. Methods: To examine the relaxation effects and mechanisms of action of TCMG-100 on rabbit cavernosal strips evaluated in an organ bath. To investigate the long-term treatment effect of TCMG-100, 8-wk administration was performed. After administration of TCMG-100, intracavernosal pressure, cyclic guanosine monophosphate and nitric oxide (NO) levels of cavernosal tissue, serum testosterone level, histological observation of collagen fiber, endothelium, smooth muscle cell, and transforming growth factor-${\beta}1$ were investigated. Results: TCMG-100 extract displayed dose-dependent relaxation effects on precontracted rabbit corporal smooth muscle. The TCMG-100-induced relaxation was significantly reduced by removing the endothelium, and treatment with an NO synthase inhibitor or NO scavenger. Eight weeks of TCMG-100 administration increased intracavernosal pressure in a rat model. The levels of cyclic guanosine monophosphate and NO in the corpus callosum and serum testosterone level were also increased by TCMG-100 treatment. Furthermore, histological evaluation of collagen, smooth muscle, and endothelium showed increases in endothelium and smooth muscle, and a decrease in transforming growth factor-${\beta}1$ expression. Conclusion: These relaxation effects on corporal smooth muscle and increased erectile function suggest that TCMG-100 might be used as an alternative herbal medicine to improve erectile function.

• Journal of Yeungnam Medical Science
• /
• v.23 no.1
• /
• pp.52-61
• /
• 2006

Background: Korean ginseng (KG) has been used as a general tonic, and for voiding dysfunction for a long time in oriental society. However, scientific basic studies on the use of KG, have been rare, especially for voiding and erectile dysfunction. This study was performed to investigate the effects of KG on voiding and erectile function by examining the effects of total saponin (TS) on the bladder, urethral and penile cavernosal smooth muscle. Materials and methods: To examine the effects of TS, NewZeland white rabbits were used to obtain tissue strips from the smooth muscle of the bladder, proximal urethra and corpus cavernosum. Adult Sprague Dawley rats were used to examine the changes in urodynamic findings and penile erection after administration of TS. Results: In proximal urethral strips, the rate of relaxation of the proximal urethra was increased from $9.0{\pm}2.9$ to $33.7{\pm}4.8%$ in a dose-dependent manner when the concentration of TS was added accumulatively from 0.25 mg/ml to 4.0 mg/ml (p<0.05). However, no significant response was observed in the bladder strips within these concentration ranges. For the corpus cavernosal strips, the rate of relaxation ranged from $5.8{\pm}2.1$ to $36.7{\pm}5.8%$, increasing in a dose-dependent manner when TS was increased from 1.0 mg/ml to 4.0 mg/ml (p<0.05). After administration of 0.1 ml of TS (32 mg/ml) in the rat, the bladder pressure was $37.5{\pm}8.5$ mmHg at $52.1{\pm}7.0$ sec. during isovolumetric bladder contraction, showing no significant differences from $35.7{\pm}7.8mmHg$ and $50.7{\pm}7.2$ sec, respectively, before treatment. However, when 0.1 ml of TS (32 mg/ml) was administered, the relative reduction of urethral pressure was $6.9{\pm}0.5mmHg$ at $62{\pm}7.5$ sec, which was significantly higher compared to $4.6{\pm}1.1mmHg$ at $45{\pm}10$ sec before treatment (p<0.05). For the cavernosal injection study, the change in intracavernosal pressure (${\Delta}ICP$) was examined after administering 0.1 ml of TS. The cumulative additions of TS at concentrations from 0.5 mg/ml to 32 mg/ml increased ${\Delta}ICP$ from $1.3{\pm}0.5$ to $21.3{\pm}7.8mmHg$ in a dose-dependent manner (p<0.05). The duration of tumescence was from $0.3{\pm}0.1$ to $5.2{\pm}0.2$ min, showing dose-dependent increase (p<0.05). Furthermore, the cumulative addition of TS at concentrations from 0.5 mg/ml upto 32 mg/ml did not cause any significant change in systemic blood pressure. Conclusion: These results suggest that ginseng improves voiding functions, which is mainly achieved by TS relaxing the proximal urethra, the most important part of the bladder outlet function. In addition, ginseng safely induced a penile erection hemodynamically by relaxing the corpus cavernosum.