• Korean Journal of Pharmacognosy
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• v.43 no.2
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• pp.184-191
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• 2012

The aim of this study was to explore the potent phosphodiesterase type 5 (PDE %) inhibitor from various herbal medicines for erectile dysfunctions. In this study, 61 herbal medicines, which were extracted with ethanol, have been investigated with PDE 5 assay using enzyme inhibitory activity on 22 species of herbal medicines. Of these, 5 species of herbal medicines, Cnidium monieri, Cuscuta chinensis, Epimedium koreanum, Morinda officinalis, and Tribulus terrestris were exhibited stronger inhibitory effect against phosphodiesterase 5 (PDE 5) among 61 species; Cnidium monieri ($IC_{50}=33.7{\mu}g/ml$), Cuscuta chinensis ($IC_{50}=65.7{\mu}g/ml$), Epimedium koreanum ($IC_{50}=90.3{\mu}g/ml$), Morinda officinalis ($IC_{50}=48.7{\mu}g/ml$) and Tribulus terrestris ($IC_{50}=32.5{\mu}g/ml$).

• Journal of Korean Neurosurgical Society
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• v.50 no.2
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• pp.109-113
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• 2011

Objective : Peripheral neuropathy is characterized by hyperalgesia, spontaneous burning pain, and allodynia. The purpose of this study was to investigate the effect of rolipram, a phosphodiesterase-4-specific inhibitor, in a segmental spinal nerve ligation model in rats. Methods : Both the L5 and L6 spinal nerves of the left side of the rats were ligated. Phosphodiesterase-4 inhibitor (rolipram) and saline (vehicle) were administered intraperitoneally. We measured mechanical allodynia using von Frey filaments and a nerve conduction study. Results : The mechanical allodynia, which began to manifest on the first day, peaked within 2 days. Multiple intraperitoneal injections of rolipram ameliorated the mechanical allodynia. Furthermore, an intraperitoneal administration of rolipram improved the development of pain behavior and nerve conduction velocity. Conclusion : This study suggests that the phosphodiesterase-4 inhibitor, rolipram, alleviates mechanical allodynia induced by segmental spinal nerve ligation in rats. This finding may have clinical implications.

• Biomolecules & Therapeutics
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• v.11 no.4
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• pp.232-237
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• 2003

The present study examined functional effects of a new selective phosphodiesterase type 5 inhibitor, 1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-thioxo-3-propyl-1H-pyrazolo[ 4,3]pyrimidin-5-yl)phenylsulphonyl]-4-methyl piperazine (KJH-1002), in the isolated rabbit corpus cavernosum (RCC). Relaxing effects of KJH-1002 were also compared with those of sildenafil, which is currently used as an oral therapy for penile erectile dysfunction. In the isolated RCC precontracted with phenylephrine, both KJH-1002 and sildenafil in the concentration range of 1 to 1000 nM, produced a comparable potentiation of the electical field stimulation-induced relaxation in a concentration-dependent manner. In the sodium nitroprusside (SNP)-induced relaxation, the $IC_{50}$/ values, concentrations of SNP required to produce a 50％ relaxation of the phenylephrine-induced contraction, were significantly decreased to the similar extent by treatments with KJH-1002 and sildenafil. The results suggest that a new selective phosphodiesterase type 5 inhibitor, KJH-1002, has an augmentative effect on penile erection comparable to that of sildenafil and can be useful for the treatment of erectile dysfunction.

• Archives of Pharmacal Research
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• v.23 no.5
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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.

• Archives of Pharmacal Research
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• v.26 no.8
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• pp.612-619
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• 2003

In this study, we evaluated the effects of oral administration of DA-8159, a selective phosphodiesterase-5 inhibitor, on the development of pulmonary hypertension (PH) induced by monocrotaline (MCT). Rats were administered either MCT (60 mg/kg) or saline. MCT-treated rats were divided into three groups and received orally administered vehicle, or 1 mg/kg or 5 mg/kg of DA-8159, twice a day for twenty-one days. The MCT group demonstrated increased right ventricular weights, medial wall thickening in the pulmonary arteries, myocardial fibrosis and the level of plasma cyclic guanosine monophosphate (cGMP), along with decreased body weight gains. However, DA-8159 markedly and dose-dependently reduced the development of right ventricular hypertrophy and medial wall thickening. DA-8159 also amplified the increase in plasma cGMP level and significantly increased the level of lung cGMP, compared with the MCT group. Although the body weight gain was still lower from the saline-treated control group, DA-8159 demonstrated a significant increase in body weight gains, in both 1 mg/kg and 5 mg/kg groups, when compared with the MCT group. In myocardial morphology, MCT-induced myocardial fibrosis was markedly prevented by DA-8159. These results suggest that DA-8159 may be a useful oral treatment option for PH.

• Applied Biological Chemistry
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• v.13 no.2
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• pp.111-129
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• 1970

As a series of studies on the nucleic acids and their related substances 210 samples were collected from 76 places such as farm soil, compost of heap, nuruk and meju to obtain microbial strains which produce 5'-phosphodiesterase. From these samples total of 758 strains were isolated by the use of dilution pour plate method. For all isolated strains primary screening of the productivity of RNA depolymerase was performed and useful strains with regard to 5'-phosphodiesterase productivities were identified. For these useful strains optimum condition, the effect of various compounds on the activity of 5'-phosphodiesterase, and the optimum condition for enzyme reaction were discussed. The quantitative of 5'-mononucleotides produced by the action of 5'-phosphodiesterase was performed using anion-exchange column chromatography and their identified was done by paper chromatography, thinlayer chromatography, ultra violet spectrophotometry, and characteristic color reaction using carbazole and schiff's reagent. (1) Penicillium citreo-viride PO 2-11 and Streptomyces aureus SOA 4-21 from soil were identified as a potent 5'-phosphodiesterase producing strains. (2) Optimum culture conditions for Penicillium citreo-viride PO 2-11 strain isolated were found to be pH 5.0 and $30^{\circ}C$, and the optimum conditions for enzyme action of 5'-phosphodiesterase were pH 4.2 and $60^{\circ}C$. Best carbon source for the production of 5'-phosphodiesterase was found to be sucrose and ammonium nitrate for nitrogen source. Addition of 0.01% corn steep liquor or yeast extract exhibited 20% increase in the amount of 5'-phosphodiesterase production compared to the control. 5'-phosphodiesterase produced by this strain was activated by $Mg^{++},\;Ca^{++},\;Zn^{++},\;Mn^{++}$ and was inhibited by EDTA, citrate, $Cu^{++},\;CO^{++}$. 5'-phosphodiesterase produced 5'-mononucleotide from RNA at a rate of 65.81%, and among the 5'-mononucleotides accumulated 5'-GMP only was found to have flavorous and the strain was also found lack of 5'-AMP deaminase. Productivity of flavorous 5'-GMP was found to be 186.7mg per gram of RNA. (3) Optimum culture canditions for the isolated Streptomyces aureus SOA 4-21 strain were pH 7.0 and $28^{\circ}C$, and the optimum conditions for the action of 5'-phosphodiesterase were pH 7.3 and $50^{\circ}C$. The best carbon source for 5'-phosphodiesterase production was found to be glucose and that of nitrogen was asparagine. Addition of 0.01% yeast extract exhibited increased productivity of 5'-phosphodiesterase by 40% compared to the non-added control. 5'-phosphodiesterase produced by this strain was activated by $Ca^{++},\;Zn^{++},\;Mn^{++}$ and was inhibited by citrate, EDTA, $Cu^{++}$. It was also found that the strain produce 5'-AMP deaminase in addition to 5'-phosphodiesterase. For this reason although decomposition rate was 63.58% the accumulation of 5'-AMP, 5'-CMP, 5'-GMP and 5'-UMP occurred by the breakdown of RNA. In the course of these reaction 5'-AMP deaminase converted 60% of 5'-AMP thus produced into 5'-IMP and flavorous 5'-mono nucleotide production was significantly increased by this strain over the above mentioned one. Production rates were found to be 171.8mg per grain of RNA for 5'-IMP and 148.2mg per gram of RNA for 5'-GMP, respectively.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.1
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• pp.26-30
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• 2016

Objective: We aimed to investigate the prevalence of erectile dysfunction (ED) and the usage of phosphodiesterase type 5 (PDE5) inhibitors for ED treatment in infertile couples. Methods: A total of 260 male partners in couples reporting infertility lasting at least 1 year were included in this study. In addition to an evaluation of infertility, all participants completed the International Index of Erectile Function (IIEF)-5 questionnaire to evaluate their sexual function. The participants were asked about their use of PDE5 inhibitors while trying to conceive during their partner's ovulatory period and about their concerns regarding the risks of PDE5 inhibitor use to any eventual pregnancy and/or the fetus. Results: Based on the IIEF-5 questionnaire, 41.5% of the participants (108/260) were classified as having mild ED (an IIEF-5 score of 17-21), while 10.4% of the participants (27/260) had greater than mild ED (an IIEF-5 score of 16 or less). The majority (74.2%, 193/260) of male partners of infertile couples had a negative perception of the safety of using a PDE5 inhibitor while trying to conceive. Only 11.1% of men (15/135) with ED in infertile couples had used a PDE5 inhibitor when attempting conception. Conclusion: ED was found to be common in the male partners of infertile couples, but the use of PDE5 inhibitors among these men was found to be very low. The majority of male partners were concerned about the risks of using PDE5 inhibitors when attempting to conceive. Appropriate counseling about this topic and treatment when necessary would likely be beneficial to infertile couples in which the male partner has ED.

• Childhood Kidney Diseases
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• v.6 no.1
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• pp.85-91
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• 2002

Purpose: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-${\beta}1$. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-${\beta}1$. Materials and Methods : Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-${\beta}1$ in renal tissue- conditioned media was measured by ELISA. Results : Masson- trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson- trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-${\beta}1$ concentration among the groups. Conclusion: A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-${\beta}1$ expression. (J Korean Soc Pediatr Nephrol 2002 ;6 : 85-91)

• Mass Spectrometry Letters
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• v.3 no.2
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• pp.50-53
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• 2012

After success of sildenafil for the treatment of erectile dysfunction, a large number of its analogues have been approved from FDA. Recently, the illegal dietary supplements which include sildenafil, vardenafil, tadalafil, or analogues of these drugs as ingredient have been widely distributed. Therefore, the determination of the residue of synthetic phosphodiesterase- 5 (PDE-5) inhibitors in dietary supplements is highly required due to indiscriminate and unintentional overdose caused nausea, chest pains, fainting and irregular heartbeat. In this paper, we report a rapid and sensitive analytical method for the simultaneous determination of nine phosphodiesterase-5 inhibitors by liquid chromatography-high resolution mass spectrometry. The present method was found to be accurate and reproducible with 40 ${\mu}g$/g of the limit of quantification for the nine PDE-5 inhibitors. The developed method can be successfully applied to the analysis of the seven illegal dietary supplements.

• The Korean Journal of Zoology
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• v.29 no.2
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• pp.79-85
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• 1986

The purpose of the present experiment is to make certain the exsistence of cAMP phosphodiesterase (PDE) in mouse oocytes and confirm its possible role on meiotic resumption. The results showed two types of cAMP in the oocytes with different Michaelis constants (Km) with specific maximum (Vmax); The Km and Vmax of one of two types of PDE were estimated at $0.14 \\pm 0.01 \\muM$ and $0.42 \\pm 0.07$ fmol cAMP hydrolyzed/oocyte/minute, and the other at $14.5 \\pm 2.0 \\muM$ and $2.2 \\pm 0.5$ fmol cAMP hydrolyzed/oocyte/minute. cAMP hydrolysis by PDE was reversibly inhibited in vitro by presence of theophylline or isobutyl-methyl-xanthine (IBMX), which is well known as an inhibitor of oocyte maturation. Consequently, it can be assumed that maturation of oocyte is affected by the high level of intracellular cAMP, and its level is well maintained by presence of PDE inhibitor, such as theophylline and IBMX.