Download PDF
Planta Med 2011; 77(14): 1575-1581
DOI: 10.1055/s-0030-1270957
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Grape Seed Proanthocyanidin Extract Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma by Downregulating Inducible Nitric Oxide Synthase

Dan-yang Zhou1 , Qiang Du2 , Ruo-ran Li3 , Mao Huang4 , Qian Zhang1 , Guo-zhen Wei1
  • 1Department of Respiratory Medicine, Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, China
  • 2Department of Respiratory Medicine, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
  • 3Department of Respiratory Medicine, Xuzhou Central Hospital, Xuzhou, China
  • 4Department of Respiratory Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
Further Information

Publication History

received Sept. 12, 2010 revised March 3, 2011

accepted March 9, 2011

Publication Date:
30 March 2011 (online)

    Permissions and Reprints

Abstract

Allergic asthma is characterized by hyperresponsiveness and inflammation of the airway with increased expression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide (NO). Grape seed proanthocyanidin extract (GSPE) has been proved to have antioxidant, antitumor, anti-inflammatory, and other pharmacological effects. The purpose of this study was to examine the role of GSPE on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice, sensitized and challenged with ovalbumin (OVA), were intraperitoneally injected with GSPE. Administration of GSPE remarkably suppressed airway resistance and reduced the total inflammatory cell and eosinophil counts in BALF. Treatment with GSPE significantly enhanced the interferon (IFN)-γ level and decreased interleukin (IL)-4 and IL-13 levels in BALF and total IgE levels in serum. GSPE also attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. The elevated iNOS expression observed in the OVA mice was significantly inhibited by GSPE. In conclusion, GSPE decreases the progression of airway inflammation and hyperresponsiveness by downregulating the iNOS expression, promising to have a potential in the treatment of allergic asthma.

Key words

asthma - airway inflammation - hyperresponsiveness - grape seed proanthocyanidin extract - inducible nitric oxide synthase

References

  • 1 Kay A B. Asthma and inflammation.  J Allergy Clin Immunol. 1991;  87 893-910
    CrossrefPubMedGoogle Scholar
  • 2 Lim K G, Mottram C. The use of fraction of exhaled nitric oxide in pulmonary practice.  Chest. 2008;  133 1232-1242
    CrossrefPubMedGoogle Scholar
  • 3 Ricciardolo F L, Nijkamp F P, Folkerts G. Nitric oxide synthase (NOS) as therapeutic target for asthma and chronic obstructive pulmonary disease.  Curr Drug Targets. 2006;  7 721-735
    CrossrefPubMedGoogle Scholar
  • 4 Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation.  Curr Drug Targets Inflamm Allergy. 2005;  4 471-479
    CrossrefPubMedGoogle Scholar
  • 5 Fernandes P D, Landgraf R G, Britto L R, Jancar S. Production of nitric oxide by airways neutrophils in the initial phase of murine asthma.  Int Immunopharmacol. 2007;  7 96-102
    CrossrefPubMedGoogle Scholar
  • 6 Islam T, Breton C, Salam M T, McConnell R, Wenten M, Gauderman W J, Conti D, Van Den Berg D, Peters J M, Gilliland F D. Role of inducible nitric oxide synthase in asthma risk and lung function growth during adolescence.  Thorax. 2010;  65 139-145
    CrossrefPubMedGoogle Scholar
  • 7 Buhl R. Local oropharyngeal side effects of inhaled corticosteroids in patients with asthma.  Allergy. 2006;  61 518-526
    CrossrefPubMedGoogle Scholar
  • 8 Hubbard R, Tattersfield A, Smith C, West J, Smeeth L, Fletcher A. Use of inhaled corticosteroids and the risk of fracture.  Chest. 2006;  130 1082-1088
    CrossrefPubMedGoogle Scholar
  • 9 Lasmar L, Camargos P, Champs N S, Fonseca M T, Fontes M J, Ibiapina C, Alvim C, Moura J A. Adherence rate to inhaled corticosteroids and their impact on asthma control.  Allergy. 2009;  64 784-789
    CrossrefPubMedGoogle Scholar
  • 10 Rachelefsky G. Inhaled corticosteroids and asthma control in children: assessing impairment and risk.  Pediatrics. 2009;  123 353-366
    CrossrefPubMedGoogle Scholar
  • 11 Nandakumar V, Singh T, Katiyar S K. Multi-targeted prevention and therapy of cancer by proanthocyanidins.  Cancer Lett. 2008;  269 378-387
    CrossrefPubMedGoogle Scholar
  • 12 Ariga T. The antioxidative function, preventive action on disease and utilization of proanthocyanidins.  Biofactors. 2004;  21 197-201
    CrossrefPubMedGoogle Scholar
  • 13 Bagchi D, Bagchi M, Stohs S J, Das D K, Ray S D, Kuszynski C A, Joshi S S, Pruess H G. Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention.  Toxicology. 2000;  148 187-197
    CrossrefPubMedGoogle Scholar
  • 14 Fine A M. Oligomeric proanthocyanidin complexes: history, structure, and phytopharmaceutical applications.  Altern Med Rev. 2000;  5 144-151
    PubMedGoogle Scholar
  • 15 Du Q, Chen Z, Zhou L F, Zhang Q, Huang M, Yin K S. Inhibitory effects of astragaloside IV on ovalbumin-induced chronic experimental asthma.  Can J Physiol Pharmacol. 2008;  86 449-457
    CrossrefPubMedGoogle Scholar
  • 16 Lee J J, Dimina D, Macias M P, Ochkur S I, McGarry M P, O'Neill K R, Protheroe C, Pero R, Nguyen T, Cormier S A, Lenkiewicz E, Colbert D, Rinaldi L, Ackerman S J, Irvin C G, Lee N A. Defining a link with asthma in mice congenitally deficient in eosinophils.  Science. 2004;  305 1773-1776
    CrossrefPubMedGoogle Scholar
  • 17 Lee M Y, Ahn K S, Kwon O K, Kim M J, Kim M K, Lee I Y, Oh S R, Lee H K. Anti-inflammatory and anti-allergic effects of kefir in a mouse asthma model.  Immunobiology. 2007;  212 647-654
    CrossrefPubMedGoogle Scholar
  • 18 Steudel W, Watanabe M, Dikranian K, Jacobson M, Jones R C. Expression of nitric oxide synthase isoforms (NOS II and NOS III) in adult rat lung in hyperoxic pulmonary hypertension.  Cell Tissue Res. 1999;  295 317-329
    CrossrefPubMedGoogle Scholar
  • 19 Miller M, Cho J Y, McElwain K, McElwain S, Shim J Y, Manni M, Baek J S, Broide D H. Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice.  Am J Physiol Lung Cell Mol Physiol. 2006;  290 L162-L169
    PubMedGoogle Scholar
  • 20 Katiyar S K. Grape seed proanthocyanidines and skin cancer prevention: inhibition of oxidative stress and protection of immune system.  Mol Nutr Food Res. 2008;  52 (Suppl. 1) S71-S76
    PubMedGoogle Scholar
  • 21 Medoff B D, Thomas S Y, Luster A D. T cell trafficking in allergic asthma: the ins and outs.  Annu Rev Immunol. 2008;  26 205-232
    CrossrefPubMedGoogle Scholar
  • 22 Lee S H, Choi S M, Sohn Y S, Kang K K, Yoo M. Effect of Oryza sativa extract on the progression of airway inflammation and remodeling in an experimental animal model of asthma.  Planta Med. 2006;  72 405-410
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Yang G, Volk A, Petley T, Emmell E, Giles-Komar J, Shang X, Li J, Das A M, Shealy D, Griswold D E, Li L. Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling.  Cytokine. 2004;  28 224-232
    CrossrefPubMedGoogle Scholar
  • 24 Moser R, Fehr J, Bruijnzeel P L. IL-4 controls the selective endothelium-driven transmigration of eosinophils from allergic individuals.  J Immunol. 1992;  149 1432-1438
    PubMedGoogle Scholar
  • 25 Schleimer R P, Sterbinsky S A, Kaiser J, Bickel C A, Klunk D A, Tomioka K, Newman W, Luscinskas F W, Gimbrone Jr M A, McIntyre B W, Bochner B S. IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1.  J Immunol. 1992;  148 1086-1092
    PubMedGoogle Scholar
  • 26 Sen C K, Bagchi D. Regulation of inducible adhesion molecule expression in human endothelial cells by grape seed proanthocyanidin extract.  Mol Cell Biochem. 2001;  216 1-7
    CrossrefPubMedGoogle Scholar
  • 27 Ma L, Gao H Q, Li B Y, Ma Y B, You B A, Zhang F L. Grape seed proanthocyanidin extracts inhibit vascular cell adhesion molecule expression induced by advanced glycation end products through activation of peroxisome proliferators-activated receptor gamma.  J Cardiovasc Pharmacol. 2007;  49 293-298
    CrossrefPubMedGoogle Scholar
  • 28 Barnes P J, Belvisi M G. Nitric oxide and lung disease.  Thorax. 1993;  48 1034-1043
    CrossrefPubMedGoogle Scholar
  • 29 Gaston B, Drazen J M, Loscalzo J, Stamler J S. The biology of nitrogen oxides in the airways.  Am J Respir Crit Care Med. 1994;  149 538-551
    CrossrefPubMedGoogle Scholar
  • 30 Moon D O, Kim M O, Lee H J, Choi Y H, Park Y M, Heo M S, Kim G Y. Curcumin attenuates ovalbumin-induced airway inflammation by regulating nitric oxide.  Biochem Biophys Res Commun. 2008;  375 275-279
    CrossrefPubMedGoogle Scholar
  • 31 Hesslinger C, Strub A, Boer R, Ulrich W R, Lehner M D, Braun C. Inhibition of inducible nitric oxide synthase in respiratory diseases.  Biochem Soc Trans. 2009;  37 886-891
    CrossrefPubMedGoogle Scholar
  • 32 Prado C M, Leick-Maldonado E A, Yano L, Leme A S, Capelozzi V L, Martins M A, Tibério I F. Effects of nitric oxide synthases in chronic allergic airway inflammation and remodeling.  Am J Respir Cell Mol Biol. 2006;  35 457-465
    CrossrefPubMedGoogle Scholar
  • 33 Houde V, Grenier D, Chandad F. Protective effects of grape seed proanthocyanidins against oxidative stress induced by lipopolysaccharides of periodontopathogens.  J Periodontol. 2006;  77 1371-1379
    CrossrefPubMedGoogle Scholar
  • 34 Bentivegna S S, Whitney K M. Subchronic 3-month oral toxicity study of grape seed and grape skin extracts.  Food Chem Toxicol. 2002;  40 1731-1743
    PubMedGoogle Scholar
  • 35 Yamakoshi J, Saito M, Kataoka S, Kikuchi M. Safety evaluation of proanthocyanidin-rich extract from grape seeds.  Food Chem Toxicol. 2002;  40 599-607
    CrossrefPubMedGoogle Scholar
  • 36 Shao Z H, Vanden Hoek T L, Xie J, Wojcik K, Chan K C, Li C Q, Hamann K, Qin Y, Schumacker P T, Becker L B, Yuan C S. Grape seed proanthocyanidins induce pro-oxidant toxicity in cardiomyocytes.  Cardiovasc Toxicol. 2003;  3 331-339
    CrossrefPubMedGoogle Scholar

Qian Zhang, PhD

Department of Respiratory Medicine
Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University

29 Xinlong Road

Changzhou 213003

China

Phone: +86 5 19 88 10 49 31

Fax: +86 5 19 88 11 55 60

Email: kezhang0601@163.com

Prof. Guo-zhen Wie

Department of Respiratory Medicine
Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University

29 Xinlong Road

Changzhou 213003

China

Phone: +86 5 19 88 10 49 31

Fax: +86 5 19 88 11 55 60

Email: guozhenwei818@sina.com

    www.thieme-connect.de/ejournals/toc/plantamedica
>