Anti-inflammatory effects of the neurotransmitter agonist Honokiol in a mouse model of allergic asthma.
Chronic airway inflammation is a hallmark of asthma, an immune-based disease with great societal impact. Honokiol (HNK), a phenolic neurotransmitter receptor (γ-aminobutyric acid type A) agonist purified from magnolia, has anti-inflammatory properties, including stabilization of inflammation in experimentally induced arthritis. The present study tested the prediction that HNK could inhibit the chronic inflammatory component of allergic asthma. C57BL/6 mice sensitized to and challenged with OVA had increased airway hyperresponsiveness to methacholine challenge and eosinophilia compared with naive controls. HNK-treated mice showed a reduction in airway hyperresponsiveness as well as a significant decrease in lung eosinophilia. Histopathology studies revealed a marked drop in lung inflammation, goblet cell hyperplasia, and collagen deposition with HNK treatment. Ag recall responses from HNK-treated mice showed decreased proinflammatory cytokines in response to OVA, including TNF-α-, IL-6-, Th1-, and Th17-type cytokines, despite an increase in Th2-type cytokines. Regulatory cytokines IL-10 and TGF-β were also increased. Assessment of lung homogenates revealed a similar pattern of cytokines, with a noted increase in the number of FoxP3(+) cells in the lung. HNK was able to alter B and T lymphocyte cytokine secretion in a γ-aminobutyric acid type A-dependent manner. These results indicate that symptoms and pathology of asthma can be alleviated even in the presence of increased Th2 cytokines and that neurotransmitter agonists such as HNK have promise as a novel class of anti-inflammatory agents in the treatment of chronic asthma.
Munroe
Melissa E
ME
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Businga
Thomas R
TR
Kline
Joel N
JN
Bishop
Gail A
GA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D006967:Hypersensitivity / Q000150:complications / Q000188:drug therapy*; D017705:Lignans / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D000498:Allyl Compounds; D010636:Phenols
D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D016207:Cytokines; D017705:Lignans; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols