title: Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice.
abstract: Zerumbone is a sesquiterpene compound isolated from the rhizome of wild ginger, Zingiber zerumbet Smith. The rhizomes of the plant are used as a spice and traditional medicine. Zerumbone was shown to possess anticarcinogenic, anti-inflammatory, and antioxidant properties. However, the antiallergic activity and the underlying mechanism of zerumbone have not been reported. Herein, we investigated the immunomodulatory effects of zerumbone on antigen-presenting dendritic cells (DCs) in vitro and its potential therapeutic effects against ovalbumin (OVA)-induced T helper 2 (Th2)-mediated asthma in mice. In the presence of zerumbone, lipopolysaccharide-activated bone marrow-derived DCs enhanced T cell proliferation and Th1 cell polarization in an allogeneic mixed lymphocyte reaction. In animal experiments, mice were sensitized and challenged with OVA, and were orally treated with different doses of zerumbone after sensitization. Circulating titers of OVA-specific antibodies, airway hyperresponsiveness to methacholine, histological changes in lung tissues, the cell composition and cytokine levels in bronchoalveolar lavage fluid, and cytokine profiles of spleen cells were assessed. Compared to OVA-induced hallmarks of asthma, oral administration of zerumbone induced lower OVA-specific immunoglobulin E (IgE) and higher IgG2a antibody production, attenuated airway hyperresponsiveness, prevented eosinophilic pulmonary infiltration, and ameliorated mucus hypersecretion. Zerumbone treatment also reduced the production of eotaxin, keratinocyte-derived chemokine (KC), interleukin (IL)-4, IL-5, IL-10, and IL-13, and promoted Th1 cytokine interferon (IFN)-γ production in asthmatic mice. Taken together, these results suggest that zerumbone exhibits an antiallergic effect via modulation of Th1/Th2 cytokines in an asthmatic mouse model.
authors.affiliation: Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Shieh
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Huei-Mei
authors.initials: HM
authors.lastname: Huang
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ching-Chiung
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Parasitology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Kwung
authors.initials: CK
authors.lastname: Fan
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: yllee@tmu.edu.tw.
authors.forename: Yueh-Lun
authors.initials: YL
authors.lastname: Lee
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D018926:Anti-Allergic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D012717:Sesquiterpenes; D007073:Immunoglobulin E; C403304:zerumbone; D010047:Ovalbumin
keywords: Asthma; Dendritic cell; Th1 cell; Th2 cell; Zerumbone