PMID- 27636508 OWN - NLM STAT- MEDLINE DCOM- 20170915 LR - 20171218 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 78 DP - 2016 Oct TI - Atractylone, an active constituent of KMP6, attenuates allergic inflammation on allergic rhinitis in vitro and in vivo models. PG - 121-132 LID - S0161-5890(16)30180-8 [pii] LID - 10.1016/j.molimm.2016.09.007 [doi] AB - 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)-kappaB/mitogen activated protein kinases (MAPKs) activation. PMACI-caused caspase-1/NF-kappaB/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 D(2), thymic stromal lymphopoietin, interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor-alpha, 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. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Kim, Hee-Yun AU - Kim HY AD - Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. FAU - Nam, Sun-Young AU - Nam SY AD - Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. FAU - Hwang, Sung-Yeoun AU - Hwang SY AD - Korea Bio Medical Science Institute, Gangnam-gu, Seoul, 06106, Republic of Korea. FAU - Kim, Hyung-Min AU - Kim HM AD - Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address: hmkim@khu.ac.kr. FAU - Jeong, Hyun-Ja AU - Jeong HJ AD - Department of Food Technology and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam, 31499, Republic of Korea. Electronic address: hjjeong@hoseo.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160913 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Plant Extracts) RN - 0 (Sesquiterpenes) RN - 0 (pyeongwee-san extract) RN - 6989-21-5 (atractylon) SB - IM MH - Animals MH - Blotting, Western MH - Cells, Cultured MH - Chromatography, Liquid MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Humans MH - Immunohistochemistry MH - Inflammation/immunology MH - Mast Cells/*drug effects MH - Mice MH - Mice, Inbred BALB C MH - Nasal Mucosa/drug effects MH - Plant Extracts/pharmacology MH - Real-Time Polymerase Chain Reaction MH - Rhinitis, Allergic/*immunology MH - Sesquiterpenes/*pharmacology MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Allergic rhinitis OT - Atractylone OT - Caspase-1 OT - Mast cells OT - Proinflammatory cytokine OT - Thymic stromal lymphopoietin EDAT- 2016/09/17 06:00 MHDA- 2017/09/16 06:00 CRDT- 2016/09/17 06:00 PHST- 2016/06/06 00:00 [received] PHST- 2016/09/07 00:00 [revised] PHST- 2016/09/08 00:00 [accepted] PHST- 2016/09/17 06:00 [pubmed] PHST- 2017/09/16 06:00 [medline] PHST- 2016/09/17 06:00 [entrez] AID - S0161-5890(16)30180-8 [pii] AID - 10.1016/j.molimm.2016.09.007 [doi] PST - ppublish SO - Mol Immunol. 2016 Oct;78:121-132. doi: 10.1016/j.molimm.2016.09.007. Epub 2016 Sep 13.