Hesperetin-7,3′-O-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio

Journal of Biomedical Science

Volumn 18, Issue 1, 2011, Pages

  Yang, You Lan ^a   Hsu, Hsin Te ^b   Wang, Kuo Hsien ^b   Han, Cheng Ying ^a   Chen, Chien Ming ^a   Chen, Chi Ming ^c   Ko, Wun Chang ^a,b  

^a TAIPEI MEDICAL UNIVERSITY   (Taiwan)

^b TAIPEI MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^c TAIPEI MEDICAL UNIVERSITY   (Taiwan)

Author keywords

Airway hyperresponsiveness; allergic asthma; chronic obstructive pulmonary disease; cytokine; hesperetin 7,3' O dimethylether; phosphodiesterase 4 inhibitor

Indexed keywords

1,3,4,5',6,6',7,12B OCTAHYDRO 1',3' DIMETHYL 2H SPIRO[BENZO[B]FURO[2,3 A]QUINOLIZINE 2,4' PYRIMIDINE] 2' ONE; 4 (3 BUTOXY 4 METHOXYBENZYL) 2 IMIDAZOLIDINONE; APREMILAST; CILOMILAST; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE 2; CYTOKINE; GAMMA INTERFERON; GSK 256066; HESPERETIN; HESPERETIN 7,3' O DIMETHYLETHER; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G2A; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; KETAMINE; METHACHOLINE; N (3,5 DICHLORO 4 PYRIDYL) [1 (4 FLUOROBENZYL) 5 HYDROXY 3 INDOLYL]GLYOXYLIC ACID AMIDE; OVALBUMIN; PHOSPHODIESTERASE I; PHOSPHODIESTERASE III; PHOSPHODIESTERASE IV; PHOSPHODIESTERASE IV INHIBITOR; PHOSPHODIESTERASE V; ROFLUMILAST; ROLIPRAM; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; XYLAZINE; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE 1; DRUG DERIVATIVE; HESPERETIN-7,3'-O-DIMETHYLETHER; HESPERIDIN; IMMUNOGLOBULIN; PDE3B PROTEIN, MOUSE;

ABDOMINAL PAIN; AIRWAY HYPERRESPONSIVENESS; AIRWAY RESISTANCE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ASTHMA; BINDING SITE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONTROLLED STUDY; DIARRHEA; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; EOSINOPHIL; FEMALE; GUINEA PIG; HEADACHE; HELPER CELL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATORY CELL; LUNG COMPLIANCE; LUNG LAVAGE; LYMPHOCYTE; MACROPHAGE; MALE; MOUSE; NAUSEA; NEUTROPHIL; NONHUMAN; PLETHYSMOGRAPHY; PRIORITY JOURNAL; PSORIASIS; RESPIRATORY TRACT DISEASE; SIDE EFFECT; TH1 CELL; TH2 CELL; WEIGHT REDUCTION; ANIMAL; BAGG ALBINO MOUSE; BLOOD CELL COUNT; BRONCHUS HYPERREACTIVITY; DISEASE MODEL; DRUG ANTAGONISM; IMMUNOLOGY; METABOLISM; PATHOPHYSIOLOGY;

MURINAE; MUS;

ANIMALS; ASTHMA; BINDING SITES; BLOOD CELL COUNT; BRONCHIAL HYPERREACTIVITY; BRONCHOALVEOLAR LAVAGE FLUID; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 1; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 3; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 4; CYTOKINES; DISEASE MODELS, ANIMAL; FEMALE; GUINEA PIGS; HESPERIDIN; IMMUNOGLOBULINS; MALE; MICE; MICE, INBRED BALB C; OVALBUMIN; PHOSPHODIESTERASE 4 INHIBITORS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; ROLIPRAM;

EID: 81055127631     PISSN: 10217770     EISSN: 14230127     Source Type: Journal    
DOI: 10.1186/1423-0127-18-84     Document Type: Article

References (57)

1. Crystal structure of phosphodiesterase 4D and inhibitor complex (1). Lee ME, Markowitz J, Lee JO, Lee H, FEBS Lett 2002 530 53 58 10.1016/S0014-5793(02) 03396-3 12387865 (Pubitemid 35248185)
2. Characterization and selective inhibition of cyclic nucleotide phosphodiesterase isozymes in canine tracheal smooth muscle. Torphy TJ, Cieslinski LB, Mol Pharmacol 1990 37 206 214 2154670 (Pubitemid 20082984)
3. Experimental studies on guanosine 3',5'-cyclic monophosphate levels and airway responsiveness of the novel phosphodiesterase type 5 inhibitor SR 265579 in guinea-pigs. Kapui Z, Schaeffer P, Mikus EG, Boronkay E, Gyurky J, Herbert JM, Pascal M, Arzneimittelforschung 1999 49 685 693 10483515 (Pubitemid 29400043)
4. Human bronchial cyclic nucleotide phosphodiesterase isoenzymes: biochemical and pharmacological analysis using selective inhibitors. de Boer J, Philpott AJ, van Amsterdam RG, Shahid M, Zaagsma J, Nicholson CD, Br J Pharmacol 1992 106 1028 1034 1393276
5. Differential pharmacologic sensitivity of cyclic nucleotide phosphodiesterase isozymes isolated from cardiac muscle, arterial and airway smooth muscle. Silver PJ, Hamel LT, Perrone MH, Bentley RG, Bushover CR, Evans DB, Eur J Pharmacol 1988 150 85 94 10.1016/0014-2999(88)90753-4 2841146
6. Improvement of therapeutic index of phosphodiesterase type IV inhibitors as anti-asthmatics. Kim E, Chun HO, Jung SH, Kim JH, Lee JM, Suh BC, Xiang MX, Rhee CK, Bioorg Med Chem Lett 2003 13 2355 2358 10.1016/S0960-894X(03)00405-0 12824033 (Pubitemid 36724981)
7. Phosphodiesterase 4 inhibitors and the treatment of asthma: where are we now and where do we go from here? Giembycz MA, Drugs 2000 59 193 212 10.2165/00003495-200059020-00004 10730545 (Pubitemid 30168507)
8. Yen KY, Pharmacology of Common Chinese Medicine (III) Taipei: National Research Institute of Chinese Medicine 1971
9. Hesperidin suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model. Wei D, Ci X, Chu X, Wei M, Hua S, Deng X, Inflammation 2011
10. Flavonoid intake and risk of chronic diseases. Knekt P, Kumpulainen J, Jarvinen R, Rissanen H, Heliovaara M, Reunanen A, Hakulinen T, Aromaa A, Am J Clin Nutr 2002 76 560 568 12198000 (Pubitemid 34920833)
11. Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships. Ko WC, Shih CM, Lai YH, Chen JH, Huang HL, Biochem Pharmacol 2004 68 2087 2094 10.1016/j.bcp.2004.06.030 15476679 (Pubitemid 39346198)
12. Assessing the emetic potential of PDE4 inhibitors in rats. Robichaud A, Savoie C, Stamatiou PB, Lachance N, Jolicoeur P, Rasori R, Chan CC, Br J Pharmacol 2002 135 113 118 10.1038/sj.bjp.0704457 11786486 (Pubitemid 34102104)
13. 2- adrenoceptor-mediated anesthesia, a behavioral correlate of emesis. Robichaud A, Stamatiou PB, Jin SL, Lachance N, MacDonald D, Laliberte F, Liu S, Huang Z, Conti M, Chan CC, J Clin Invest 2002 110 1045 1052 12370283
14. The exhaustive O-methylation of quercetin. Gomm AS, Nierenstein M, J Am Chem Soc 1931 53 4408 4411 10.1021/ja01363a021
15. Multiple cyclic nucleotide phosphodiesterase activities from rat brain. Thompson WJ, Appleman MM, Biochemistry 1971 10 311 316 10.1021/bi00778a018 4321663
16. Effects of selective inhibitors on cyclic nucleotide phosphodiesterases of rabbit aorta. Ahn HS, Crim W, Romano M, Sybertz E, Pitts B, Biochem Pharmacol 1989 38 3331 3339 10.1016/0006-2952(89)90631-X 2554921 (Pubitemid 19254124)
17. Isolation and characterization of bovine cardiac muscle cGMP-inhibited phosphodiesterase: a receptor for new cardiotonic drugs. Harrison SA, Reifsnyder DH, Gallis B, Cadd GG, Beavo JA, Mol Pharmacol 1986 29 506 514 3010079 (Pubitemid 16068905)
18. The identification of a new cyclic nucleotide phosphodiesterase activity in human and guinea-pig cardiac ventricle. Implications for the mechanism of action of selective phosphodiesterase inhibitors. Reeves ML, Leigh BK, England PJ, Biochem J 1987 241 535 541 3036066 (Pubitemid 17234191)
19. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Bradford MM, Anal Biochem 1976 72 248 254 10.1016/0003-2697(76)90527-3 942051
20. Stereospecific binding of the antidepressant rolipram to brain protein structures. Schneider HH, Schmiechen R, Brezinski M, Seidler J, Eur J Pharmacol 1986 127: 105 115 (Pubitemid 16023615)
21. 3H]rolipram. Zhao Y, Zhang HT, O'Donnell JM, J Pharmacol Exp Ther 2003 305 565 572 10.1124/jpet.102.047407 12704225 (Pubitemid 36459171)
22. Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge. Kanehiro A, Ikemura T, Makela MJ, Lahn M, Joetham A, Dakhama A, Gelfand EW, Am J Respir Crit Care Med 2001 163 173 184 11208644 (Pubitemid 32095268)
23. Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model. Kim DY, Park JW, Jeoung D, Ro JY, Eur J Pharmacol 2009 612 98 105 10.1016/j.ejphar.2009.03.078 19356734
24. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen GL, Irvin CG, Gelfand EW, Am J Respir Crit Care Med 1997 156 766 775 9309991 (Pubitemid 27396413)
25. Flow cytometric detection of antigen-specific cytokine responses in lung T cells in a murine model of pulmonary inflammation. Winterrowd GE, Chin JE, J Immunol Methods 1999 226 105 118 10.1016/S0022-1759(99)00049-6 10410976 (Pubitemid 29336535)
26. Short-term smoke exposure attenuates ovalbumin-induced airway inflammation in allergic mice. Melgert BN, Postma DS, Geerlings M, Luinge MA, Klok PA, van der Strate BW, Kerstjens HA, Timens W, Hylkema MN, Am J Respir Cell Mol Biol 2004 30 880 885 14722223 (Pubitemid 38736913)
27. Asthma. Busse WW, Lemanske RF Jr, N Engl J Med 2001 344 350 362 10.1056/NEJM200102013440507 11172168 (Pubitemid 32107645)
28. Where asthma and hypersensitivity pneumonitis meet and differ: noneosinophilic severe asthma. Bogaert P, Tournoy KG, Naessens T, Grooten J, Am J Pathol 2009 174 3 13 10.2353/ajpath.2009.071151 19074616
29. Lipoprotein I, a TLR2/4 ligand modulates Th2-driven allergic immune responses. Revets H, Pynaert G, Grooten J, De Baetselier P, J Immunol 2005 174 1097 1103 15634935 (Pubitemid 40094307)
30. Regulatory T cells, a potent immunoregulatory target for CAM researchers: the ultimate antagonist (I). Vojdani A, Erde J, Evid Based Complement Alternat Med 2006 3 25 30 10.1093/ecam/nek022 16550220 (Pubitemid 43999648)
31. The role of IL-13 in established allergic airway disease. Taube C, Duez C, Cui ZH, Takeda K, Rha YH, Park JW, Balhorn A, Donaldson DD, Dakhama A, Gelfand EW, J Immunol 2002 169 6482 6489 12444158 (Pubitemid 36903499)
32. Leukotrienes mediate murine bronchopulmonary hyperreactivity, inflammation, and part of mucosal metaplasia and tissue injury induced by recombinant murine interleukin-13. Vargaftig BB, Singer M, Am J Respir Cell Mol Biol 2003 28 410 419 10.1165/rcmb.2002-0032OC 12654629 (Pubitemid 36399362)
33. Integrative inflammation pharmacology: Asthma. Tucker J, Fanta CH, Principles of Pharmacology-The Pathophysiologic Basis of Drug Therapy Philadelphia: Lippincott Williams & Wilkins, Golan DE, Tashjian AH Jr, Armstrong EJ, Galanter JM, Armstrong AW, Arnaout RA, Rose HS, 2005 695 705
34. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG, J Exp Med 1996 183 195 201 10.1084/jem.183.1.195 8551223 (Pubitemid 26028759)
35. A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. Clayton E, Bardi G, Bell SE, Chantry D, Downes CP, Gray A, Humphries LA, Rawlings D, Reynolds H, Vigorito E, Turner M, J Exp Med 2002 196 753 763 10.1084/jem.20020805 12235209
36. Impaired B and T cell antigen receptor signaling in p110 PI 3-kinase mutant mice. Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, Pearce W, Meek SE, Salpekar A, Waterfield MD, Smith AJ, Vanhaesebroeck B, Science 2002 297 1031 1034 12130661 (Pubitemid 34856039)
37. Inhibition of phosphoinositide 3-kinase delta attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model. Lee KS, Lee HK, Hayflick JS, Lee YC, Puri KD, FASEB J 2006 20 455 465 10.1096/fj.05-5045com 16507763 (Pubitemid 44933322)
38. Interleukin (IL)-4-independent induction of immunoglobulin (Ig)E, and perturbation of T cell development in transgenic mice expressing IL-13. Emson CL, Bell SE, Jones A, Wisden W, McKenzie AN, J Exp Med 1998 188 399 404 10.1084/jem.188.2.399 9670052 (Pubitemid 28357768)
39. The immunoglobulin class switch: beyond "accessibility". Snapper CM, Marcu KB, Zelazowski P, Immunity 1997 6 217 223 10.1016/S1074- 7613(00)80324-6 9075922 (Pubitemid 27148588)
40. Molecular processes that regulate class switching. Stavnezer J, Curr Top Microbiol Immunol 2000 245 127 168 10.1007/978-3-642-59641-4-6 10533321
41. Vasodilators and nitric oxide synthase. Westfall DP, Gerthoffer WT, Webb RC, Human Pharmacology Molecular to Clinical St. Louis: Mosby, Brody TM, Larner J, Minneman KP, 1998 239 247
42. Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lipworth BJ, Lancet 2005 365 167 175 10.1016/S0140-6736(05) 17708-3 15639300 (Pubitemid 40091808)
43. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. Hatzelmann A, Schudt C, J Pharmacol Exp Ther 2001 297 267 279 11259554 (Pubitemid 32242587)
44. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, Rabe KF, Lancet 2009 374 695 703 10.1016/S0140-6736(09)61252-6 19716961
45. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ, Lancet 2009 374 685 694 10.1016/S0140-6736(09)61255-1 19716960
46. Anti-inflammatory potential of the selective phosphodiesterase 4 inhibitor N-(3,5-dichloro-pyrid-4-yl)- [1-(4-fluorobenzyl)-5-hydroxy-indole-3- yl]-glyoxylic acid amide (AWD 12-281), in human cell preparations. Draheim R, Egerland U, Rundfeldt C, J Pharmacol Exp Ther 2004 308 555 563 14610230 (Pubitemid 38134217)
47. In vivo efficacy in airway disease models of N-(3,5-dichloropyrid-4-yl)- [1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281), a selective phosphodiesterase 4 inhibitor for inhaled administration. Kuss H, Hoefgen N, Johanssen S, Kronbach T, Rundfeldt C, J Pharmacol Exp Ther 2003 307 373 385 10.1124/jpet.103.053942 12944497 (Pubitemid 37151930)
48. The phosphodiesterase 4 inhibitor AWD 12-281 is active in a new guinea-pig model of allergic skin inflammation predictive of human skin penetration and suppresses both Th1 and Th2 cytokines in mice. Hoppmann J, Baumer W, Galetzka C, Hofgen N, Kietzmann M, Rundfeldt C, J Pharm Pharmacol 2005 57 1609 1617 16354405 (Pubitemid 41752275)
49. Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking? Giembycz MA, Br J Pharmacol 2008 155 288 290 18660832
50. PDE4 inhibitors: a review of current developments (2005-2009). Pages L, Gavalda A, Lehner MD, Expert Opin Ther Pat 2009 19 1501 1519 10.1517/13543770903313753 19832118
51. Is PDE4 too difficult a drug target? Higgs G, Curr Opin Investig Drugs 2010 11 495 498 20419594
52. The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma. Singh D, Petavy F, Macdonald AJ, Lazaar AL, O'Connor BJ, Respir Res 2010 11 26 34 10.1186/1465-9921-11-26 20193079
53. An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Gottlieb AB, Strober B, Krueger JG, Rohane P, Zeldis JB, Hu CC, Kipnis C, Curr Med Res Opin 2008 24 1529 1538 10.1185/030079908X301866 18419879 (Pubitemid 351741586)
54. Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety. Burgin AB, Magnusson OT, Singh J, Witte P, Staker BL, Bjornsson JM, Thorsteinsdottir M, Hrafnsdottir S, Hagen T, Kiselyov AS, Stewart LJ, Gurney ME, Nat Biotechnol 2010 28 63 70 10.1038/nbt.1598 20037581
55. Insights into the physiological functions of PDE4 from knockout mice. Jin SL, Richter W, Conti M, Cyclic Nucleotide Phosphodiesterases in Health and Disease Boca Raton: CRC Press, Beavo JA, Francis SH, Houslay MD, 2007 323 346
56. Phosphodiesterase inhibitors in airways disease. Fan CK, Eur J Pharmacol 2006 533 110 117 10.1016/j.ejphar.2005.12.059 16458289 (Pubitemid 43348344)
57. Robichaud A, Savoie C, Stamatiou PB, Tattersall FD, Chan CC: PDE4 inhibitors induce emesis in ferrets via a noradrenergic pathway. Neuropharmacology 2001, 40:262-269.