Abstract
The natural product oleanolic acid is commonly found in a variety of medicinal plants. It is a triterpenoid compound known for its anti-inflammatory effects as well as various other pharmacological properties. The aim of the current study was to use a mouse model of allergic asthma to investigate whether oleanolic acid has anti-asthmatic effects, and if so, to determine the mechanism of these effects. Oleanolic acid suppressed eosinophil infiltration, allergic airway inflammation, and Penh, which occurred by suppressing the production of IL-5, IL-13, IL-17, and ovalbumin-specific IgE through the upregulation of T-bet and Foxp3, and the downregulation of GATA-3 and RORγt. The therapeutic effect of oleanolic acid was due to suppression of Th2 cytokines (IL-5 and IL-13), B cell-dependent production of OVA-specific IgE, and Gr-1 expression through the T-bet, GATA-3, retinoic acid-related orphan receptor γ t (RORγ t) and forkhead box p3 (Foxp3) transcription pathways. It is therefore reasonable to suggest that the anti-inflammatory and anti-asthmatic effects of oleanolic acid may be exerted through inhibition of the GATA-3 and RORγt pathways.
Keywords:
Asthma; GATA-3; IL-17; Oleanolic acid; RORγt; Th2.
Copyright © 2013 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allergens / immunology
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Animals
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Anti-Asthmatic Agents / pharmacology*
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Anti-Asthmatic Agents / therapeutic use
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Asthma / drug therapy
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Asthma / immunology*
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Asthma / pathology
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Asthma / physiopathology
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Bronchial Hyperreactivity / drug therapy
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Bronchial Hyperreactivity / immunology*
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Bronchial Hyperreactivity / pathology
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Bronchial Hyperreactivity / physiopathology
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Bronchoalveolar Lavage Fluid / cytology
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CD4-Positive T-Lymphocytes / immunology
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Cell Line, Tumor
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Cytokines / genetics
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Cytokines / immunology
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Eosinophils / immunology
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Female
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology
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GATA3 Transcription Factor / genetics
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GATA3 Transcription Factor / immunology
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Lung / immunology
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Lung / pathology
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Mice
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Mice, Inbred BALB C
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Neutrophils / immunology
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Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
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Oleanolic Acid / pharmacology*
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Oleanolic Acid / therapeutic use
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Ovalbumin / immunology
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Pneumonia / drug therapy
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Pneumonia / immunology*
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Pneumonia / pathology
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Pneumonia / physiopathology
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / immunology
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Th2 Cells / immunology
Substances
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Allergens
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Anti-Asthmatic Agents
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Cytokines
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Nuclear Receptor Subfamily 1, Group F, Member 3
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Oleanolic Acid
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Ovalbumin