Grape seed proanthocyanidin extract attenuates allergic inflammation in murine models of asthma

J Clin Immunol. 2012 Dec;32(6):1292-304. doi: 10.1007/s10875-012-9742-8. Epub 2012 Jul 27.

Abstract

Background: Antioxidants have been suggested to alleviate the pathophysiological features of asthma, and grape seed proanthocyanidin extract (GSPE) has been reported to have powerful antioxidant activity.

Purpose: This study was performed to determine whether GSPE has a therapeutic effect on allergic airway inflammation in both acute and chronic murine model of asthma.

Methods: Acute asthma model was generated by intraperitoneal sensitization of ovalbumin (OVA) with alum followed by aerosolized OVA challenges, whereas chronic asthma model was induced by repeated intranasal challenges of OVA with fungal protease twice a week for 8 weeks. GSPE was administered by either intraperitoneal injection or oral gavage before OVA challenges. Airway hyperresponsiveness (AHR) was measured, and airway inflammation was evaluated by bronchoalveolar lavage (BAL) fluid analysis and histopathological examination of lung tissue. Lung tissue levels of various cytokines, chemokines, and growth factors were analyzed by quantitative polymerase chain reaction and ELISA. Glutathione assay was done to measure oxidative burden in lung tissue.

Results: Compared to untreated asthmatic mice, mice treated with GSPE showed significantly reduced AHR, decreased inflammatory cells in the BAL fluid, reduced lung inflammation, and decreased IL-4, IL-5, IL-13, and eotaxin-1 expression in both acute and chronic asthma models. Moreover, airway subepithelial fibrosis was reduced in the lung tissue of GSPE-treated chronic asthmatic mice compared to untreated asthmatic mice. Reduced to oxidized glutathione (GSH/GSSG) ratio was increased after GSPE treatment in acute asthmatic lung tissue.

Conclusion: GSPE effectively suppressed inflammation in both acute and chronic mouse models of asthma, suggesting a potential role of GSPE as a therapeutic agent for asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / pathology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokine CCL11 / genetics
  • Chemokine CCL11 / immunology
  • Chronic Disease
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Gene Expression
  • Glutathione / metabolism
  • Grape Seed Extract / pharmacology*
  • Inflammation
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukin-5 / genetics
  • Interleukin-5 / immunology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / pathology
  • Lung / drug effects*
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Proanthocyanidins / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • Interleukin-13
  • Interleukin-5
  • Proanthocyanidins
  • Interleukin-4
  • Ovalbumin
  • Glutathione