• 생약학회지
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• 제38권1호
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• pp.50-55
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• 2007

This study was designed to investigate the effects KH-204 on erectile dysfunction in hyperlipidemic rat. KH-204 has been evaluated antihyperlipidemic and antierectile dysfunction effects on experimental hyperlipidemic rats induced by high fat diet. After oral administration of the water extract KH-204 (50, 100, 200, 300 mg/kg) to hyperlipidemic rats for 8 weeks, the variables including body weight, total cholesterol, HDL and LDL levels in serum, the expression of eNOS and nNOS in penis were measured. And erectile function was determined by measurement of intracavernosal pressure (ICP) and maximal arterial pressure (MAP) after electrical stimulation of the cavernosal nerve. Oral administration of KH-204 significantly inhibited the increases of serum total cholesterol and LDL-cholesterol levels and the decreased of serum HDL-cholesterol levels in hyperlipidemic rats induced by high fat diet. The penile expression level of the two enzyme (eNOS, nNOS) were increased significantly after oral administration of the KH-204 50 mg/kg. Erectile function after 10 volts stimulation was significantly decreased in the hyperlipidemic rat compared with the normal rat, but increased in KH-204 group compared with hyperlipidemic group. These results suggest that KH-204 is effective for erectile dysfunction in hyperlipidemia.

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

• Journal of Pharmaceutical Investigation
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• 제34권2호
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• pp.107-114
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• 2004

External lyogels containing prostaglandin $E_1$ ethyl ester $(PGE_1-EE)$, a prodrug of prostaglandin $E_1\;(PGE_1)$ as a therapeutic agent for erectile dysfunction, were formulated to overcome the aqueous instability and enhance the percutaneous absorption. Lyogels of $PGE_1-EE$ were prepared with ethanol (EtOH)/proplyene glycol (PG) cosolvent system as a vehicle, cineol as an enhancer, and hydroxypropylcellusose as a gelling agent. In vitro percutaneous absorption studies were performed to determine the rate of $PGE_1$ absorption through rat or hairless mouse skin. The permeability of $PGE_1-EE$ lyogel with enhancer was 16-fold greater than that of lyogel without enhancer. Cosolvent produced 9-fold increase in percutaneous absorption. Pharmacodynamic effects of lyogels were evaluated in mature male cats in terms of intracavernosal pressure (ICP). Lyogels containing 0.1 % of $PGE_1-EE$ showed higher ICP compared to intraurethral preparation of $PGE_1$ (1 %) and enhancer-free control lyogel. The shelf-life $(t_{10%})$ of lyogel at refrigerated condition $(4^{\circ}C)$ was calculated as 928 days, which is 4.2 times longer than that of control hydrogel. As a result, $PGE_1-EE$ was formulated successfully to a lyogel system with a selective enhancer and cosolvent system for the topical delivery of $PGE_1$.

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

• 대한본초학회지
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• 제30권6호
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• pp.69-75
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• 2015

Objectives : This study was designed to investigate effects of the combination with Korean Red Ginseng (Panax ginseng C.A. Meyer), Gastrodia Rhizoma (Gastrodia elata Blume) and Polygoni Multiflori Radix (Polygonum multiflorum Thunberg) on metabolic disorders including cholesterol and erectile dysfunction in hyperlipidemia rats.Methods : Animals were divided into six groups; Control with normal diet, high fat/cholesterol-diet (HFCD), fluvastatin, Korean Red Ginseng treated (KRG), and the combination treated (Korean Red Ginseng, Gastrodia Rhizoma and Polygoni Multiflori Radix; 1:1:1 for KGP1 and 2:1:1 for KGP2). The experimental groups initially received HFCD for 10 weeks and then treated orally with fluvastatin, KRG, KGP1 and KGP2 during the final 6 weeks. Erectile function was determined by the measurements of intracavernosal pressure (ICP) and maximal arterial pressure (MAP) after electrical stimulation of the cavernosal nerve.Results : KGP2 decreased the level of total cholesterol and LDL cholesterol in the sera of HFCD rats without no changes of body weights. KRG, KGP1 and KGP2 decreased the level of C-reactive protein (CRP) levels except of fluvastatin, synthetic HMG-CoA reductase inhibitor. KRG, KGP1 and KGP2 significantly increased the ICP, ICP/MAP ratio, area under the curve (AUC) compared with those of normal rat. Morphometric analyses showed that KRG, KGP1 and KGP2 increased the volume of smooth muscle and the regular arrangement of collagen fibers in corpus cavernosum of HFCD rats. The penile expression of eNOS was increased by KRG, KGP1 and KGP2.Conclusions : Based on these results, we suggest that the combination with Korean Red Ginseng, Gastrodia Rhizoma and Polygoni Multiflori may improve hyperlipidemia through regulating the lipid profiles and erectile dysfunction in rats.

• 한국식품영양과학회지
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• 제36권5호
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• pp.548-553
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• 2007

저자들은 일반 흰쥐를 1.5% cholesterol과 0.25% cholic acid, 우지 25% 첨가한 식이로 고지혈증을 유발시킨 후 KH-305를 8주간 경구투여하여 혈중 cholesterol과 HDL-C, LDL-C 등을 측정, 지질대사에 미치는 영향을 알아보았다. 또한, 최대해면체 내압과 내피 관련 NOS 발현정도를 측정하여 음경발기 촉진 및 지속에 미치는 영향을 알아보았다. 그 결과 KH-305를 투여한 모든 그룹에서 고지방식이 그룹보다 총 cholesterol 수치와 LDL-C를 낮추었으며 HDL-C의 수치를 높였다. 최대해면체 내압에서는 KH-305 투여 그룹이 고지방식이 그룹보다 최대해면체 내압에 이르는 시간이 짧았고 최대해면체 내압의 수치가 높았으며 이 중 300mg/kg일 경우 가장 효과가 좋았다. 또한, KH-305 모든 투여 그룹은 고지방식이 그룹과 비교해 볼 때 모든 그룹에서 eNOS와 nNOS의 발현이 뚜렷이 증가되었다. 따라서, 혈중 cholesterol을 낮추면서 NOS의 발현을 증가, 최대해면체 내압이 큰 KH-305는 고지혈증으로 유발된 발기부전에 효능이 있는 약물이 될 수 있으리라 사료된다.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.173-178
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• 2000

The purpose of this work is to develop a transurethral suppository containing prostaglandin $E_1\;(PGE_1)$, which stabilizes the drug, gives no irritation to physiological body and enhances the erectile response of $PGE_1.\;PGE_1$ transurethral suppositories were prepared with various amounts of compositions such as saturated polyglycolysed glyceride $(Suppocire^{\circledR}\;AP,\;SAP)$, polyoxyethylene hydrogenated castor oil (HCO-50) and ethanol. The melting points, viscosities and $PGE_1$ release of the suppositories were investigated. Ocular irritation test was carried out after application of $PGE_1$ suppository to rabbit's eye. The intracavernous pressure (ICP), penile length and duration of erectile response were determined after transurethral administration of $PGE_1$ suppository and compared with those after intracavernosal injection of $PGE_1$ solution to cats. HCO-50 hardly affected the melting points and viscosities of $PGE_1$ suppositories. Additionally, $PGE_1$ transurethral suppositories, whose melting point ranges was $34-35^{\circ}C$, was speedily melted in physiological body. HCO-50 significantly decreased the dissolution rates of $PGE_1$ from the suppositories. Dissolution mechanism analysis showed the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppositories by Fickian diffusion. The release rate of $PGE_1$ from $PGE_1$ suppository [PGE1/SAP/HCO-50/ethanol (1/94.5/2.5/2%)] was about 80% within 2 h. This $PGE_1$ suppository gave no significant irritation to the ocular tissue, expecting that it gave no irritation to the urethral tissue less sensive than ocular tissue. Furthermore, $PGE_1$ in this suppository was stable at $4^{\circ}C$ for 2 years. This suppository increased the ICP and penile erection similar to those of injectable $PGE_1$ solution. However, it gave 2.5-fold increased duration of erectile response than injectable $PGE_1$ solution. Our results suggested that it gave more effective erectile response than injectable $PGE_1$ solution in cats. It is concluded that this $PGE_1$ suppository with good safety, excellent stability and enhanced erectile response, could be a more effective and convenient transurethal delivery system of $PGE_1$.

• Molecules and Cells
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• 제41권6호
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• pp.553-561
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• 2018

Icariside II (ICA II) is used in erectile dysfunction treatment. Adipose tissue-derived stem cells (ADSCs) are efficient at improving erectile function. This study aimed to explore the action mechanism of ADSCs in improving erectile function. ADSCs were isolated from the adipose tissues of rats. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8) assay. The expressions of mRNA and protein were determined separately through qRT-PCR and western blot. The endogenous expressions of related genes were regulated using recombinant plasmids and cell transfection. A Dual-Luciferase Reporter Assay was performed to determine the interaction between miR-34a and STAT3. Rat models with bilateral cavernous nerve injuries (BCNIs) were used to assess erectile function through the detection of mean arterial pressure (MAP) and intracavernosal pressure (ICP). ICA II promoted ADSCs' proliferation and differentiation to Schwann cells (SCs) through the inhibition of miR-34a. Suppressed miR-34a promoted the differentiation of ADSCs to SCs by upregulating STAT3. ICA II promoted the differentiation of ADSCs to SCs through the miR-34a/STAT3 pathway. The combination of ICA II and ADSCs preserved the erectile function of the BCNI model rats. ADSCs treated with ICA II markedly preserved the erectile function of the BCNI model rats, which was reversed through miR-34a overexpression. ICA II promotes the differentiation of ADSCs to SCs through the miR34a/STAT3 pathway, contributing to erectile function preservation after the occurrence of a cavernous nerve injury.

• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.52-61
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• 2006

이상의 결과를 종합하면, 인삼 총사포닌은 본 실험의 조건에서 배뇨개선 효과가 있으며 이에 관여하는 총사포닌의 주 효능은 근위부요도를 이완시킴으로써 이루어지는 것으로 생각된다. 그리고 인삼 총사포닌은 혈류역동학적으로 안전하게 음경해면체 평활근을 이완시켜 음경발기를 유발시키는 것으로 생각된다.