title: Atractylone, an active constituent of KMP6, attenuates allergic inflammation on allergic rhinitis in vitro and in vivo models.
abstract: KMP6 (Pyeongwee-San) is a Korean Medicine used to treat gastrointestinal disorders. Recently, we reported KMP6 had beneficial effects on allergic inflammatory diseases. The aim of this study was to evaluate the effects of atractylone (Atr), a constituent of KMP6, on allergic rhinitis (AR) and to identify the mechanism responsible for these effects. The anti-allergic inflammatory effects of Atr were evaluated on phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells and in an ovalbumin (OVA)-induced AR animal model using Western blotting, quantitative real-time PCR, ELISA, and immunohistochemistry methods. In HMC-1 cells, Atr and KMP6 attenuated PMACI-caused proinflammatory cytokine production and mRNA expression. We found that PMACI induced caspase-1/nuclear factor (NF)-κB/mitogen activated protein kinases (MAPKs) activation. PMACI-caused caspase-1/NF-κB/MAPKs activations were attenuated by Atr and KMP6. In AR animal model, Atr and KMP6 reduced AR clinical symptoms and biomarkers including rub scores, total IgE, histamine, prostaglandin D2, thymic stromal lymphopoietin, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor-α, cyclooxygenase-2, intercellular adhesion molecule-1, and macrophage inflammatory protein-2. In addition, Atr and KMP6 attenuated eosinophils and mast cells invasions into nasal mucosa tissues and diminished mast cell-derived caspase-1 activation. These results indicate that Atr is an active constituent of KMP6 and a potential therapeutic agent for AR.
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Hee-Yun
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Nam
authors.affiliation: Korea Bio Medical Science Institute, Gangnam-gu, Seoul, 06106, Republic of Korea.
authors.forename: Sung-Yeoun
authors.initials: SY
authors.lastname: Hwang
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address: hmkim@khu.ac.kr.
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Food Technology and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam, 31499, Republic of Korea. Electronic address: hjjeong@hoseo.edu.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D065631:Rhinitis, Allergic / Q000276:immunology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry
chemical_list: D010936:Plant Extracts; D012717:Sesquiterpenes; C562348:pyeongwee-san extract; C046196:atractylon
keywords: Allergic rhinitis; Atractylone; Caspase-1; Mast cells; Proinflammatory cytokine; Thymic stromal lymphopoietin