• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.1
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• pp.24-29
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• 2018

In order to define the effect of Torilis Fructus(TF) extract which has been used for the treatment of erectile dysfunction, experiments were carried out by organ bath study, histochemical and immunohistochemical methods. First, in the organ bath study, when TF extract was administered to the maxillary contracted corpus cavernosum by PE ($10^{-6}M$), there was a significant relaxation effect on corpus cavernosum at concentration of 1, $3mg/m{\ell}$. Compared with the absence of $\text\tiny{L}$-NNA pretreatmen, pretreatment of $\text\tiny{L}$-NNA was inhibited the relaxation effect of penile corpus cavernosum. In the immunohistochemical study, the eNOS positive reaction was significantly increased, and the PDE5 positive reaction was significantly decreased due to the administration of TF extract. Therefore, it show that the TF enhances the production of eNOS and NO, inhibits PDE5 which blocks the action of increased cGMP, relaxes the corpus cavernosum. So TF relaxes the corpus cavernosum and it can be used as a safer erectile dysfunction treatment.

• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.665-679
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• 2022

Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

• Mass Spectrometry Letters
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• v.3 no.1
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• pp.15-17
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• 2012

Eighteen of the PDE-5 inhibitors and their analogues were analyzed using GC-EI-MS. Fourteen of them could be identified by simple GC-MS method without derivatization, but hydroxyhongdenafil, hydroxyvardenafil, xanthoanthrafil and mirodenafil could not be identified without derivatization for the high polarity due to the presence of hydroxyl groups. N,O-bis(trimethylsilyl) trifluoroacetamide (BSTFA) and N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), widely used trimethylsilyl (TMS) derivatizing reagents, were used to improve the sensitivity of the hydroxylated analogues. And the analytes could be identified by GC-MS after the derivatization.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.286-286
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• 1994

Thrombin (0.25 U/ml : TB), 소-피부 collagen (200 $\mu\textrm{g}$/ml : CG), adenosine 5'-diphesphate (4,0 $\times$ $10^{-5}$M : ADP), 및 epinephrine (4,0 $\times$ 10 $^{-5}$M : EPI)의 가토-혈소판 응집과 단백인산화작용에 미치는 PDE-I (3-isobutyl-1-methylxanthine : IBMX, 및 KR 30075), amitriptyline (AP), chlorpromazine (CP), 및 sodium nitrogrosside (SNP)의 염향을 비교-검토하였다. 그 결과, KR은 2,2 $\times$ $10^{-7}$M 이하의 $IC_{50}$/에서 EPI > ADP > CG > TB 순으로 각각을 억제하였으며, SNP 보다도 강하였고; KR-30075보다 약하나 IBMX, AP, 및 CP도 각 응집재의 작용을 억제하였으며 특히 EPI에 대하여 $10^{-8}$M 이하의 $IC_{50}$/에서 유의한 억제력을 보였다. 각 응집제들은 41 kD 인산화는 유의하게 증가시키며 47 kD와 20 kD 단백인산화는 감소시켰는데; 모든 항응집성 약물이 41 kD 인산화-증가는 유의하게 억제하였다, 아울러, AP와 CP는 47 kD 단백인산화-감소에 영향을 미치지 않았으나 20 kD 단백인산화-감소는 억제하였다. PDE-I (IBMX와 KR)와 SNP는 47 kD와 20 kD 단백인산화-감소를 다소 약화시켰으며, 43 kD와 22 kD 단백인산화를 KR > IBMX > SNP순으로 유의하게 증가시켰고, KR의 22 kD 단백인산화작용은 현저하였다.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1571-1579
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• 2016

We investigated the effect of peanut sprout extract (PSE) on andropause symptoms. PSE was evaluated for impotency and benign prostatic hyperplasia via phosphodiesterase (PDE) or 5-alpha reductase II inhibition assay. Inhibition of PDE and 5-alpha reductase II activities in PSE was significantly higher than that of the non-treated control. To investigate the effects of testosterone levels by PSE, we performed cell media test using TM3 cells. Production of testosterone in TM3 cells was elevated by PSE. These results indicate that PSE was able to alleviate andropause symptoms.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.119-123
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• 1991

${\beta}-Adrenoceptor$ binding study of ${\beta}-agonist$ ((-)NE), ${\beta}-antagonists$ $(({\pm})\;propranolol,\;labetalol)$ and PDE inhibitors (imazodan, KR-30045, KR-30075 etc.) was performed using $(-)-[^3H]-DHA$, as a $non-{\beta}_1/{\beta}_2$ selective radioligand. In saturation studies, $K_d$ and $B_{max}$ of $(-)-[^3H]-DHA$ to ${\beta}-adrenoceptors$ in rat left ventricle in which both ${\beta}_1$ and ${\beta}_2$ receptors coexist were determined to be $1.5{\pm}0.43\;nM$ and $22.0{\pm}0.9\;fmol/mg$ protein, respectively. $({\pm})Propranolol$, labetalol and (-)NE competed for $(-)-[^3H]-DHA$ binding sites in an essentialy monophasic manner with $Ki=17.0{\pm}0.40\;nM,\;57.3{\pm}1.30\;nM,\;and\;1.57{\pm}0.95\;{\mu}M$, respectively. All of PDE inhibitors inhibited the $(-)-[^3H]-DHA$ binding by only below 10% even at the high concentration of $10^{-3}M$. The present results suggest that propranolol, labetalol and NE are $non-{\beta}_1/{\beta}_2$ selective antagonists and agonist, respectively. Additionally, this study shows that imazodan and new synthesized PDE inhibitors may hardly have the affinities to ${\beta}-adrenoceptors$ in cardiac muscle.

• Mass Spectrometry Letters
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• v.6 no.2
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• pp.38-42
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• 2015

Roflumilast analogs are a group of drugs which act as selective photodiesterase (PDE-4) inhibitor for the treatment severe chronic pulmonary disease associated with chronic brochnonities. Structural identification of degradation products using high resolution mass spectrometry and theoretical investigation by density functional theory have been successfully carried out on roflumilast to identify four degradation products namely, 3,5-dichloropyridin-4-amine, N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)-3-hydroxy benzamide, N-(3,5-dichloropyridin-4-yl)-3-(cyclopropylmethoxy)-4-(difluoromethoxy) benzamide and 3-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-4-(difluoro methoxy) benzamide, generated in alkali, acidic and oxidative conditions.

• Natural Product Sciences
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• v.23 no.3
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• pp.169-174
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• 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 Pharmaceutical Investigation
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• v.40 no.2
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• pp.117-123
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• 2010

Ibudilast, 3-isobutyryl-2-isopropyrazolo[1,5-a]pyridine, is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It preferentially inhibits PDE 3A, PDE4, PDE10 and PDE11 as well as a number of the other PDE families, albeit to a lesser extent. Ibudilast is used clinically to treat bronchial asthma and cerebrovascular disorders. Thes e clinical uses are based on the ability of ibudilast to inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The purpose of the present study was to evaluate the bioequivalence of two ibudilast capsules, Ketas capsule (Handok Pharmaceuticals Co., Ltd.) and Pinatos capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of ibudilast from the two ibudilast formulations was tested using KP Apparatus method with various dissolution media. Twenty six healthy male subjects, 23.31${\pm}$1.09 years in age and 70.45${\pm}$8.51 kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single capsule containing 10 mg as ibudilast was orally administered, blood samples were taken at predetermined time intervals and the concentrations of ibudilast in serum were determined using HPLC/UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Ketas, were 6.99%, -2.48% and 9.93% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.8791~log 1.1861 and log 0.8347~log 1.1199 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Pinatos capsule was bioequivalent to Ketas capsule.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.5
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• pp.308-313
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• 2016

The purpose of this study is to investigate the effects of Oja-Shingiwhan(OS) in contracted corpus cavernosum smooth muscle and its mechanism. To evaluate the relaxation of OS in contracted corpus cavernosum, OS was treated in strips which were precontracted with phenylephrine(PE). To examine its mechanism, OS was treated into corporal strips contracted by PE after pretreatment of Nω-nitro-L-arginine(L-NNA) and compared with non-pretreatment of _L-NNA. In calcium chloride(Ca²⁺)-free krebs solution, Ca²⁺ 1 mM was treated into corporal strips contracted by PE after pretreatment of OS and compared with non-pretreatment of OS. action were measured by histochemical, immunohistochemical methods. OS significantly affected on the relaxation of corporal strips, and the relaxation effects were inhibited by pretreatment of L-NNA. Contractions induced by Ca²⁺ influx were inhibited by pretreatment of OS in Ca²⁺-free krebs solution. OS increased eNOS positive reaction in corpus cavernosum, but decreased PDE-5 positive reaction. These result suggest that the effect of OS in contracted corpus cavernosum smooth muscle are shown by suppressing extracellular Ca²⁺ influx and increase of eNOS, NO production and decrease of PDE-5.