Park Hyo-Hyun, Lee Soyoung, Oh Jae-Min, Lee Myeung-Su, Yoon Kwon-Ha, Park Byoung Hyun, Kim Jeong Woo, Song Haheon, Kim Sang-Hyun
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, South Korea.
Pharmacol Res. 2007 Jan;55(1):31-7. doi: 10.1016/j.phrs.2006.10.002. Epub 2006 Oct 10.
Mast cells play an important role in the pathogenesis of allergic diseases through the release of inflammatory mediators such as histamine, cysteinyl leukotrienes, cytokines, and chemokines. Flavonoids, like fisetin are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. The aim of our study was to examine whether fisetin modulates inflammatory reaction in stimulated human mast cells (HMC-1). Fisetin decreased phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated gene expression and production of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-4, IL-6, and IL-8 in HMC-1 cells. Fisetin inhibited PMACI-induced phosphorylation of p38 mitogen-activated protein kinase, extracellular-regulated kinase, and c-Jun N-terminal kinase. In addition, fisetin suppressed nuclear factor (NF)-kappaB activation induced by PMACI, leading to expression of IkappaB-alpha phosphorylation and degradation. Fisetin suppressed powerful induction of NF-kappaB promoter-mediated luciferase activity. These pharmacological actions of fisetin produce new suggestion that fisetin is a potential medicine for treatment of inflammatory diseases through the down-regulation of mast cell activation.
肥大细胞通过释放组胺、半胱氨酰白三烯、细胞因子和趋化因子等炎症介质，在过敏性疾病的发病机制中发挥重要作用。黄酮类化合物，如非瑟酮，是具有抗氧化、细胞保护和抗炎作用的天然存在的分子。我们研究的目的是检验非瑟酮是否能调节人肥大细胞（HMC-1）的炎症反应。非瑟酮可降低佛波酯12-肉豆蔻酸酯13-乙酸酯加钙离子载体A23187（PMACI）刺激的HMC-1细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-4、IL-6和IL-8的基因表达及产生。非瑟酮抑制PMACI诱导的p38丝裂原活化蛋白激酶、细胞外调节激酶和c-Jun氨基末端激酶的磷酸化。此外，非瑟酮抑制PMACI诱导的核因子（NF）-κB活化，导致IκB-α磷酸化和降解的表达。非瑟酮抑制NF-κB启动子介导的荧光素酶活性的强烈诱导。非瑟酮的这些药理作用提示非瑟酮可能是一种通过下调肥大细胞活化来治疗炎症性疾病的潜在药物。
