Kim Hee-Yun, Nam Sun-Young, Hwang Sung-Yeoun, Kim Hyung-Min, Jeong Hyun-Ja
Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
Korea Bio Medical Science Institute, Gangnam-gu, Seoul, 06106, Republic of Korea.
Mol Immunol. 2016 Oct;78:121-132. doi: 10.1016/j.molimm.2016.09.007. Epub 2016 Sep 13.
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 D, 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.
KMP6(平胃散)是一种用于治疗胃肠道疾病的韩医方剂。最近,我们报道KMP6对过敏性炎症性疾病有有益作用。本研究的目的是评估KMP6的成分苍术酮(Atr)对过敏性鼻炎(AR)的影响,并确定其作用机制。采用蛋白质免疫印迹法、定量实时聚合酶链反应、酶联免疫吸附测定和免疫组织化学方法,在佛波醇12-肉豆蔻酸酯13-乙酸酯和钙离子载体A23187(PMACI)刺激的人肥大细胞系HMC-1细胞以及卵清蛋白(OVA)诱导的AR动物模型中评估Atr的抗过敏炎症作用。在HMC-1细胞中,Atr和KMP6减弱了PMACI诱导的促炎细胞因子产生和mRNA表达。我们发现PMACI诱导半胱天冬酶-1/核因子(NF)-κB/丝裂原活化蛋白激酶(MAPKs)激活。Atr和KMP6减弱了PMACI诱导的半胱天冬酶-1/NF-κB/MAPKs激活。在AR动物模型中,Atr和KMP6减轻了AR临床症状和生物标志物,包括抓挠评分、总免疫球蛋白E、组胺、前列腺素D、胸腺基质淋巴细胞生成素、白细胞介素(IL)-1β、IL-4、IL-5、IL-6、IL-13、肿瘤坏死因子-α、环氧化酶-2、细胞间黏附分子-1和巨噬细胞炎性蛋白-2。此外,Atr和KMP6减弱了嗜酸性粒细胞和肥大细胞向鼻黏膜组织的浸润,并减少了肥大细胞衍生的半胱天冬酶-1激活。这些结果表明,Atr是KMP6的活性成分,是一种潜在的AR治疗药物。