Tag: Phosphodiesterase

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A short review on structure and role of cyclic-3′,5′-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool.

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A short review on structure and role of cyclic-3′,5′-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool.

J Res Pharm Pract. 2015 Oct-Dec;4(4):175-181

Authors: Eskandari N, Mirmosayyeb O, Bordbari G, Bastan R, Yousefi Z, Andalib A

Abstract
Cyclic nucleotide phosphodiesterases (PDEs) are known as a super-family of enzymes which catalyze the metabolism of the intracellular cyclic nucleotides, cyclic-3′,5′-adenosine monophosphate (cAMP), and cyclic-3′,5′-guanosine monophosphate that are expressed in a variety of cell types that can exert various functions based on their cells distribution. The PDE4 family has been the focus of vast research efforts over recent years because this family is considered as a prime target for therapeutic intervention in a number of inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, and it should be used and researched by pharmacists. This is because the major isoform of PDE that regulates inflammatory cell activity is the cAMP-specific PDE, PDE4. This review discusses the relationship between PDE4 and its inhibitor drugs based on structures, cells distribution, and pharmacological properties of PDE4 which can be informative for all pharmacy specialists.

PMID: 26645022 [PubMed – as supplied by publisher]

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Hesperidin-3′-o-methylether is more potent than hesperidin in phosphodiesterase inhibition and suppression of ovalbumin-induced airway hyperresponsiveness.

Hesperidin-3′-o-methylether is more potent than hesperidin in phosphodiesterase inhibition and suppression of ovalbumin-induced airway hyperresponsiveness.

Evid Based Complement Alternat Med. 2012;2012:908562

Authors: Yang YL, Hsu HT, Wang KH, Wang CS, Chen CM, Ko WC

Abstract
Hesperidin is present in the traditional Chinese medicine, “Chen Pi,” and recently was reported to have anti-inflammatory effects. Therefore, we were interested in comparing the effects of hesperidin and hesperidin-3′-O-methylether on phosphodiesterase inhibition and airway hyperresponsiveness (AHR) in a murine model of asthma. In the present results, hesperidin-3′-O-methylether, but not hesperidin, at 30??mol/kg (p.o.) significantly attenuated the enhanced pause (P(enh)) value, suppressed the increases in numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and BALF, and enhanced the level of total IgG(2a) in the serum of sensitized and challenged mice, suggesting that hesperidin-3′-O-methylether is more potent than hesperidin in suppression of AHR and immunoregulation. The different potency between them may be due to their aglycons, because these two flavanone glycosides should be hydrolyzed by ?-glucosidase after oral administration. Neither influenced xylazine/ketamine-induced anesthesia, suggesting that they may have few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, hesperidin-3′-O-methylether is more potent in phosphodiesterase inhibition and suppression of AHR and has higher therapeutic (PDE4(H)/PDE4(L)) ratio than hesperidin. Thus, hesperidin-3′-O-methylether may have more potential for use in treating allergic asthma and chronic obstructive pulmonary disease.

PMID: 23082087 [PubMed – in process]

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Therapeutic Potential of ASP3258, a Selective Phosphodiesterase 4 Inhibitor, on Chronic Eosinophilic Airway Inflammation.

Therapeutic Potential of ASP3258, a Selective Phosphodiesterase 4 Inhibitor, on Chronic Eosinophilic Airway Inflammation.

Pharmacology. 2012;90(3-4):223-32

Authors: Kobayashi M, Kubo S, Shiraki K, Iwata M, Hirano Y, Ohtsu Y, Takahashi K, Shimizu Y

Abstract
We investigated and compared the pharmacological effects of a PDE4 inhibitor ASP3258 (3-[4-(3-chlorophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid), with those of roflumilast, the most clinically advanced PDE4 inhibitor known. ASP3258 inhibited human PDE4A, 4B, 4C, and 4D with respective IC(50) values of 0.036, 0.050, 0.45, and 0.035 nmol/l, all approximately 3-6 times more potent than roflumilast. ASP3258 inhibited LPS-induced TNF-? production and PHA-induced IL-5 production in human whole blood cells with respective IC(50) values of 110 and 100 nmol/l, both approximately 10 times less potent than roflumilast. Repeatedly administered ASP3258 and roflumilast both suppressed chronic airway eosinophilia induced by repeated exposure to ovalbumin in Brown Norway rats with respective ED(50) values of 0.092 and 0.17 mg/kg. We also evaluated the toxicological profiles of ASP3258. Although PDE4 inhibitors induce emesis by mimicking the pharmacological action of an ?(2)-adrenoceptor antagonist, repeated administration of ASP3258 (3 mg/kg) had no such inhibitory effect on rats anesthetized with ?(2) – adrenoceptor agonist. PDE4 inhibitors are also known to induce vascular injury in rats. Although repeatedly administered ASP3258 (3 and 10 mg/kg) significantly increased plasma fibrinogen, a biomarker for toxicity, 1 mg/kg of ASP3258 did not. These results suggest that ASP3258 is an attractive PDE4 inhibitor for treating chronic eosinophilic airway inflammation due to asthma.

PMID: 23038661 [PubMed – in process]

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