• Natural Product Sciences
• /
• 제23권3호
• /
• 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.

• 대한임상검사과학회지
• /
• 제54권4호
• /
• pp.307-315
• /
• 2022

중년 이후 많은 환자들이 배뇨 후 요실금을 앓고 있지만 아직 적절한 치료가 이뤄지지 않고 있다. 몇 가지 병태생리학적 기전이 제안되었지만 우리가 주목한 기전은 구해면체근과 해면체 조직의 위축으로 인한 요도의 확장이었다. 본 연구의 목적은 해면체와 요도의 해부학적 변화를 관찰하여 배뇨 후 요실금의 기전을 규명하는 것으로 8주령의 SD 수컷 랫드 그룹과 24개월 이상 된 SD 수컷 랫드 그룹으로 나누었다. 전체 음경에 대한 구부요도 및 해면체 면적의 비율은 두 그룹 간 통계적으로 유의하였다(P<0.05). 평활근 함량과 배뇨 후 요실금의 기전(nNOS, α-SMA)과 관련된 매개변수는 두 그룹 간 유의한 차이가 있었으며(P<0.05), 본 연구의 결과는 배뇨 후 요실금 연구에 기여할 것으로 기대된다.

• 동의생리병리학회지
• /
• 제27권5호
• /
• pp.625-630
• /
• 2013

Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men worldwide. ED is now considered an early manifestation of atherosclerosis, and consequently, a precursor of systemic vascular disease. Lycii fructus extracts (LFE) were administered for 4 weeks to assess the improving effects on ED. Animals were divided into one normal group and four LFE-treated groups (0, 0.3, 0.6, and 1.2 g/kg). We induced ED in the study animals by oral administration of 20% ethanol instead of water everyday for 4 weeks. This study was designed to investigate the effects of LFE on the mRNA levels of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) expression; NO levels of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP); blood profile; and erectile response of the corpus cavernosum of the rat penis. The libido of the LFE-administered male rats was higher than that of the ethanol control group. The erectile response of the corpus cavernosum was restored after LFE administration, to a level similar to the normal group. In addition, the iNOS in the corpus cavernosum of the male rats administered LFE decreased. In contrast, compared to the control group, LFE-administered male rats showed increased eNOS, NO and cGMP levels in the corpus cavernosum. These results indicate that LFE effectively restored ethanol-induced ED in male rats.

• 생약학회지
• /
• 제38권3호통권150호
• /
• pp.239-244
• /
• 2007

The herbal formulation (KH-204) mainly consisted of the fruits of Lycium chinense, Cornus officinalis, Rubus coreanus, Cuscuta chinensis and Schizandra chinensis. We investigated the effects of this herbal formulation on the penile erection and corpus cavernosum of spontaneous hypertensive male Rats (SHR). We used male SHR aged 16 weeks as a model of hypertension. The treatment groups received once a day oral doses KH-204 100 and 300 mg/kg per day for 4 weeks. Distilled water was administered in the control group. To investigate the penile erection, intracavernosal pressure (ICP) and mean arterial pressure (MAP) were recorded in all groups. We analyzed the distribution of NOS by immunohistochemical staining and the expression of nNOS, eNOS concentration in the isolated corpus cavernosum by western blotting. In the control group, ICP/MAP ratio was $14.9{\pm}1.4%$ after pelvic nerve stimulation. ICP/MAP ratio was markedly increased in the treatment group with KH-204 100, 300 mg/kg, compared with control group. Immunohistochemical staining for NOS showed that eNOS and nNOS was stained as brown color. Compared with the control group, NOS activities of KH-204 100, 300 mg/kg were increased significantly. Also the penile expression levels of nNOS, eNOS in KH-204 100, 300 mg/kg treatment group were more increased significantly than control group by western blotting. This study showed that KH-204 enhances the penile erection and the level of eNOS and nNOS expression of penile corpus cavernosum of male SHR.

• 한국임상약학회지
• /
• 제21권1호
• /
• 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.

• Archives of Pharmacal Research
• /
• 제23권5호
• /
• pp.471-476
• /
• 2000

DA-8159, a new phosphodiesterase 5 inhibitor, was assessed for its erectogenic potential by a penile erection test in rats, the relaxation of isolated rabbit corpus cavernosum (CC), and estimation of the intracavernous pressure (ICP) in the anesthetized dog. Oral administration of DA-8159 (0.3 to 1 ${\mu}g/kg$ ) increased the number of erections in rats with increasing dosage, with the highest penile erection index at 10 ${\mu}g/kg$ DA-8159 induced the relaxation of phenylephrine (PHE)-induced contractions in the rabbit CC and decreased the $IC_{50}$ of the nitric oxide donor sodium nitroprusside (SNP) in a dose-dependent fashion. In pentobarbital-anesthetized dogs, the intravenous administration of DA-8159 (1~300 ${\mu}g/kg$ ) potentiated the increase in ICP induced by the intracavernosal SNP in a dose-related manner. These findings suggest that DA-8159 has significant therapeutic potential in the treatment of erectile dysfunction.

• 한국식품영양과학회지
• /
• 제35권7호
• /
• pp.847-852
• /
• 2006

KH204가 음경해면체 이완과 생식기능에 미치는 영향을 규명하기 위해 효능을 실험한 결과 토끼의 음경해면체를 $1{\times}10^{-6}M$ pheylephrine으로 수축시킨 후 KH204를 61, 183 및 549 mg/L의 축적용량으로 처리하여 각각 6.8, 10.1 및 16%의 용량의존적인 이완효과를 관찰하였다. 흰쥐를 이용한 생식기능 실험은 KH204를 61, 183 및 549 mg/kg으로 10주간 장기투여에서 생식장기인 고환조직의 중량 및 정자수 증가에 유의한 효과를 나타내었다. 정자 형태검사는 대조군과 비슷한 수치로 나타내어 고농도로 장기투여에도 정자군과 비슷한 수치로 나타내어 고농도로 장기투여에도 정자 기형에 문제가 없음을 확인하였다. 이상의 결과로 KH204가 특별한 부작용이 없이 음경해면체를 농도의존적으로 이완시키는 효과가 있어, 음경발기를 개선시키는 효과뿐만 아니라 고환성 원인 또는 정자생산 기능부전으로 보이는 남성불임에서 또한 효능이 있음을 시사하였다.

• The Korean Journal of Physiology
• /
• 제29권1호
• /
• pp.61-67
• /
• 1995

The extract of Ginkgo bibloba (EGb) is a complex mixture of natural products from the Ginkgo leaves and clinically used for the treatment of cerebral and peripheral circulatory disturbances due to its combined activity of several vasoactive principles. In this study we investigated the action of EGb and its mechanism in isolated rabbit corporal smooth muscle to evaluate the possibility of using this material as a pharmacoerecting agent. Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. EGb began to exert an relaxing effect at 1 mg/ml in the submaximally precontracted muscle strips with phenylephrine $(PHE,\;5{\times}10^{-6}\;M)$; causing concentration-dependent relaxation with maximal effect at $3{\sim}5\;mg/ml$. That relaxation was partially inhibited by removal of the smooth muscle endothelium or by pretreatment with a NO scavenger, pyrogallol $(10^{-4}\;M)$ or the guanylate cyclase inhibitor, methylene blue $(10^{-4}\;M)$. Pretreatment with EGb (3 mg/ml) inhibited PHE- $(5{\times}10^{-6}\;M)$ or KCI- (20 and 40 mM) induced contraction of muscle strip. In calcium-free high potassium solution EGb depressed the basal tone of the depolarized muscle strip and inhibited calcium-induced contraction when $CaCl_2$ $(10^{-4}\;M)$ was added. These results suggest that EGb relaxes rabbit corpus cavernosal smooth muscle through multiple action mechanisms that include increasing the release of nitric oxide from the corporal sinusoidal endothelium, sequestration of intracytosolic calcium, and maybe a hyperpolarizing action.

• Archives of Pharmacal Research
• /
• 제25권6호
• /
• 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.

• Natural Product Sciences
• /
• 제22권1호
• /
• pp.46-52
• /
• 2016

Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men and considered to be an early symptom of atherosclerosis and a precursor of various systemic vascular disorders. The aim of the present study was to prepare ginsenoside Re enriched fraction (GS-F3K1, ginsenoside Re 10%, w/w) from ginseng berries flesh and to investigate the enhanced activities of GS-F3K1 on alcohol-induced ED. GS-F3K1 was prepared by the continuous liquid and solid separating centrifugation and circulatory ultrafiltration from ginseng berries flesh. GS-F3K1 was administered for 5 weeks in ethanol-induced ED rat by oral administration of 20% ethanol. To investigate the effects of GS-F3K1 on ED model, the levels of nitrite expression, cyclic guanosine monophosphate (cGMP) and erectile response of the penile corpus cavernosum of rat were measured. The erectile response of the corpus cavernosum was restored after GS-F3K1 administration, to a level similar to the normal group. The level of nitrite and cGMP expression in the corpus cavernosum of GS-F3K1-administered male rats was increased significantly compared to positive control group. GS-F3K1 from ginseng berries should effectively restore ethanol-induced ED in male rats and could be developed as a new functional food for the elderly men.