• Title/Summary/Keyword: Phosphodiesterase 7

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Screening of Anti-atopic Herbs Having Phosphodiesterase 4 and 7 Inhibition (Phosphodiesterase 4와 7에 대한 억제 기전을 갖는 아토피 억제 물질의 탐색)

  • Yoon, Won Ho;Lee, Keyong Ho
    • Korean Journal of Pharmacognosy
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    • v.45 no.3
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    • pp.268-274
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    • 2014
  • The aim of this study is to explore the potent phosphodiesterase 4 and 7 inhibitor from various herbal medicines for atopy treatment. In this study, 51 kinds of each herbal medicine, which were extracted with ethanol, was carried out the screening of PDE 4 and 7 inhibition using enzyme inhibitory assay. Of these, 8 species of herbal medicines, Rubus coreanus, Duchesnea chrysantha, Alisma orientale, Rehmannia glutinosa, Angelica dahurica, Thuja orientalis, Astragalus membranaceus and Perilla frutescens were screened as potential inhibitor against PDE 4 and 7. Among 8 species, Duchesnea chrysantha showed poteinial anti-atopic effect on DNCB-induced atopic model. Duchesnea chrysantha extract decreased serum IgE and histamine release significantly.

Studies on Degradation of Nucleic acid and Related Compounds by Microbial Enzymes (미생물 효소에 의한 핵산 및 그의 관련물질의 분해에 관한 연구)

  • Kim, Sang-Soon
    • 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.

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Screening of Herbal Medicines for Phosphodiesterase 5 Inhibitor (약용식물로 부터의 Phosphodiesterase 5 저해제 검색)

  • Lee, Keyong-Ho;Kim, Byeong-Soo;Rhee, Ki-Hyeong
    • 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 ($IC_{50}=32.5{\mu}g/ml$).

Cell Biological Studies on the Mechanism of Development and Differentiation Ⅷ 2. Effects of Peptide on cAMP Level in Corn Endosperm (생체발생 및 문화기구의 세포생물학적 연구 Ⅷ 2. 옥수수 배젖에서 Peptide가 cAMP Level에 미치는 영향)

  • Young Dong Cho
    • Journal of Plant Biology
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    • v.27 no.1
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    • pp.7-13
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    • 1984
  • Activities of corn endosperm adenylate cyclase and phosphodiesterase were found right after germination, and phosphodiesterase activity was shown to increase steadily. Protease activity was also found. Corn peptide fraction purified by using Sephadex G-25 column was shown to enhance corn phosphodiesterase activity buy inhibit bovine phosphodiesterase activity. And the fraction inhibits corn adenylate cyclase activity. Trypsintreated peptide fraction was shown to enhance phosphodiesterase activity 80% compared to that of native peptide fraction. However, in case of DNase phosphodiesterase was shown to be innocuous. According to cumulative results, it is more likely that peptide fraction produced by protease inhibits adenylate cyclase activity and enhance phosphodiesterase, decreasing cAMP level.

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Expression of the cAMP Phosphodiesterase 7A1 Gene by Endoplasmic Reticulum Stress (소포체스트레스에 의한 cAMP phosphodiesterase 7A1 유전자의 발현)

  • Kwon, Ki-Sang;Kwon, Young-Sook;Kwon, O-Yu
    • Journal of Life Science
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    • v.22 no.2
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    • pp.281-284
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    • 2012
  • This study demonstrated that upregulation of gene expression of endoplasmic reticulum (ER) stress chaperones (Bip, ERp29, calnexin, and PDI), ER stress sensors (PERK, ATF6, and Ire1), and cAMP phosphodiesterase 7A1 (cAMP PDE7A1) was induced by ER stresses in FRTL5 cells. While removing A23187 from the culture medium restored upregulation of cAMP PDE7A1 gene expression, removal of thapsigargin did not recover its expression. In addition, cAMP PDE7A1 gene expression was strongly inhibited by treatment with A23187 combined with thyroid stimulating hormone (TSH). The results are the first to show that ER stress induces cAMP PDE7A1 gene expression.

Effects of a New Selective Phosphodiesterase Type 5 Inhibitor, KJH-1002, on the Relaxation of Rabbit Corpus Cavernosum Tissue

  • Cho, Eun-Young;Chung, Sung-Hyun;Kim, Joong-Hyup;Kim, Dong-Hyun;Jin, Cang-Bae
    • 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.

Inhibition of Platelet Activation by Marine Sterols from Octocorals (팔방산호충류에서 분리한 해양 스테롤 화합물의 혈소판 응집 억제작용)

  • Park, Young-Hyun;Chang, Sung-Keun;Seo, Young-Wan;Shin, Jong-Heon
    • YAKHAK HOEJI
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    • v.41 no.5
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    • pp.547-553
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    • 1997
  • The purpose of this investigation was to determine the inhibition on $Na^+,\;K^+$-ATPase, cyclic AMP phosphodiesterase and platelet activation by marine sterols isolated from octocorals. Three marine polyhydroxysterols, 7${\alpha},\;8{\alpha}-epoxy-3b{\beta},\;5{\alpha},\;6{\alpha}-trihydroxycholestane (1),\;24-methyl-7{\alpha},\;8{\alpha}-epoxy-3{\beta},\;5{\alpha},\;6{\alpha}-trihydroxycholest-22-ene (2),\;and\;7{\alpha},\;8{\alpha}-epoxy-3{\beta},\;5{\alpha},\;6{\alpha}-trihydroxycholest-22-ene (3)$, were isolated from the Gorgonian Acabaria undulata. Five marine sterols(compound 4, 5, 6, 7, 8) were isolated from the soft coral Alcyonium gracillimum. Three marine polyhydroxysterols (1, 2, 3) and pregna-1. 20-diene-3-one (8) exhibit a potent inhibitory effect on rabbit platelet aggregation induced by collagen and thrombin. Those polyhydroxysterols also exhibit a potent inhibitory effect on cyclic AMP phosphodiesterase. Compound 6 with an unusual cyclic enolether exhibit a inhibitory effect on $Na^+,\;K^+$-ATPase.

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The Effects of Okwada on the Lung Fibrosis Mouse Model (오과다가 쥐의 폐섬유화 모델의 치료에 미치는 영향)

  • Lee, Hai-Ja
    • The Journal of Pediatrics of Korean Medicine
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    • v.23 no.3
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    • pp.233-240
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    • 2009
  • Objectives To evaluate that Okwada affected which factors for treatment of lung fibrosis. Methods Bleomycin induced lung fibrosis model made in mice. After Okwada lyophilized, power sample obtained and melt in distilled water. Okwada solution administered mice through oral route on 21 days after bleomycin instillation and this procedure performed once a day for 7 days. We divided by three groups; normal (control), bleomycin induced lung fibrosis without treatment (experimental), bleomycin induced lung fibrosis with treatment (treatment). On six weeks after bleomycin instillation, mice sacrificed and removed lung. Weperformed Western blot analysis for TGF-beta, phosphodiesterase 5A, interleukin (4,5,13) and compared therapeutic effects of Okwada. Results On western blot analysis, all normal and experimental mice detected TGF-beta, phosphodiesterase 5A, interleukin 4,5,13. The amount of band of TGF-beta, phosphodiesterase 5A, interleukin 5 in experimental and treatment group was similar. However, interleukin 4,13 of treatment group decreased compared with experimental group. Conclusions Okwada would be effected the lung fibrosis through suppression of interleukin 4,13.

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Inhibition of Calmodulin-Dependent Calcium-ATPase and Phosphodiesterase by Various Cyclopeptides and Peptide Alkaloids from the Zizyphus Species

  • Hwang, Keum-Hee;Han, Yong-Nam;Han, Byung-Hoon
    • Archives of Pharmacal Research
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    • v.24 no.3
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    • pp.202-206
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    • 2001
  • The effects of various sedative cyclopeptides and peptide alkaloids from the Zizyphus species on calmodulin-dependent $Ca^{2+}$ -ATPase and phosphodiesterase were Investigated. Calmodulin-induced activation of $Ca^{2+}$-ATPase was strongly inhibited by sanjoinine-A dialdehyde (IC_{50}$, 2.3$\mu\textrm{m}$), -Ah1 (IC_{50}$, 4.0$\mu\textrm{m}$), -A (IC, 4.6$\mu\textrm{m}$), and -G2 (IC_{50}$, 7.2$\mu\textrm{m}$), while calmodulin-induced activation of phosphodiesterase was strongly inhibited by both deachuine- S10 (IC_{50}$, 4.9$\mu\textrm{m}$) and sanjoinine-D (IC_{50}$, 9.0$\mu\textrm{m}$). The inhibitory activity of the various cyclopeptides and peptide alkaloids on $Ca^{2+}$-ATPase was found to correlate well with their Sedative activity.

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Vasorelaxant properties of cyclic nucleotide phosphodiesterase inhibitors in rat aorta (흰쥐 대동맥에서 cyclic nucleotide phosphodiesterase 억제제들의 혈관 이완 특성)

  • Kang, Hyung-sub;Choi, Cheol-ho;Kim, Jin-shang
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.615-624
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    • 2003
  • Vascular smooth muscle relaxation is modulated by an increase in cGMP subsequent to nitric oxide (NO) production by endothelial cells. The effects of cAMP and cGMP phosphodiesterase (PDE) inhibitors were investigated in phenylephrine-precontracted rat aorta rings by using the specific inhibitors of PDE I, III, IV and V as relaxing agents (calmodulin-activated PDE inhibitors, IBMX and $W_7$, type I; cAMP-specific PDE inhibitors, milrinone, type IV; Ro 20-1724, type III and cGMP-specific PDE inhibitor, zaprinast, type V). All the PDE inhibitors produced a concentration-dependent relaxation in the ring with intact endothelium (+E). Except for milrinone, all the PDE inhibitors-induced relaxations were inhibited by removal of extracellular $Ca^{2+}$, $N^G$-nitro-L-arginine, $N^G$-nitro-L-arginine methyl ester, methylene blue (MS) or nifedipine. The specific PDE I and PDE IV inhibitors both produced endothelium-independent relaxations which were inhibited by MS in -E rings. However, zaprinast had no effect in -E rings. Except for milrinone, sodium nitroprusside (a NO donor)-induced relaxation was significantly augmented by all PDE inhibitors in +E rings. The results suggest that I) the vasorelaxant properties of IBMX, $W_7$, Ro 20-1724 and zaprinast are dependent on endothelium or on interaction with $Ca^{2+}$ regulation, 2) each PDE is differently distributed in vascular tissues (endothelial and smooth muscle cells), 3) the vasodilations of PDE inhibitors are due to the increase of cAMP and cGMP formation through inhibition of cAMP- and cGMP-PDE and 4) the vasodilation action of milrinone does not involve in endothelial-cyclic nucleotide system.