ABSTRACT
BACKGROUND: Many people are troubled by allergic inflammation including ocular allergic diseases, anaphylaxis, allergic rhinitis, atopic dermatitis, and eczema. Consequently, finding medications for use in allergic inflammation therapy is crucial in human health. Manoalide, a marine natural product isolated as an anti-bacterial metabolite from Luffariella variabilis, is a calcium channel blocker. However, its latent ability as an anti-allergic inflammatory agent has not yet been reported. Our research aimed to elucidate whether manoalide exerts an anti-allergic inflammatory effect in the human mast cell line, HMC-1. METHODS: Herein, we investigated the immunoregulatory effects and molecular mechanisms of manoalide in HMC-1 cells. RESULTS: Manoalide significantly alleviated secretion of the inflammatory cytokines interleukin (IL)-1ß, thymic stromal lymphopoietin, tumor necrosis factor-α, IL-6, and IL-8 via blockage of caspase-1 without cytotoxicity in activated HMC-1 cells. Activation of nuclear factor-κB increased by mast cell stimulation was attenuated by treatment with manoalide. In addition, we demonstrated that manoalide treatment remarkably attenuated the activation of mitogen-activated protein kinases in activated-HMC-1 cells. CONCLUSIONS: Taken together, our findings indicate manoalide has an anti-allergic inflammatory role, and we propose that manoalide might have potential as a novel anti-allergic inflammatory agent.
Subject(s)
Anti-Allergic Agents/pharmacology , Calcium Channel Blockers/pharmacology , Mast Cells/drug effects , NF-kappa B/antagonists & inhibitors , Terpenes/pharmacology , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Humans , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/immunology , Inflammation Mediators/metabolism , Mast Cells/immunology , Mast Cells/metabolism , NF-kappa B/immunology , NF-kappa B/metabolismABSTRACT
OBJECTIVE: AST2017-01 is developed to be used for treatment and prevention of allergic diseases and composed of processed-Cordyceps militaris and processed-Rumex crispus. But, effect of AST2017-01 remains unclear in an allergic rhinitis (AR). So, this study aimed to explore the effects of AST2017-01 in ovalbumin (OVA)-induced AR animal model. METHODS: OVA-induced AR animals were orally administered AST2017-01 and chrysophanol, an active component of AST2017-01 for 10 days. RESULTS: In mice with AR, AST2017-01 and chrysophanol markedly decreased number of rubs, IgE, histamine, thymic stromal lymphopoietin, tumor necrosis factor-α, interleukin (IL)-1ß, IL-4, IL-5, and IL-13 in serum or nasal mucosa tissues. Moreover, activities and protein levels of caspase-1 were markedly diminished by oral administration of AST2017-01 and chrysophanol. Declines of macrophage inflammatory protein-2, intercellular adhesion molecules-1, eosinophil, and mast cells were also noted in nasal mucosa tissues of AST2017-01 and chrysophanol groups. CONCLUSIONS: Taken together, these findings indicate that AST2017-01 has an anti-allergic effect as a therapeutic agent or functional food for treating and preventing AR.