Kim Min-Jong, Kim Yeon-Yong, Choi Young-Ae, Baek Moon-Chang, Lee Byungheon, Park Pil-Hoon, Shin Tae-Yong, Kwon Taeg Kyu, Khang Dongwoo, Kim Sang-Hyun
CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea.
Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
Front Pharmacol. 2018 Jun 7;9:591. doi: 10.3389/fphar.2018.00591. eCollection 2018.
Mast cells are major effector cells for allergic responses that act by releasing inflammatory mediators, such as histamine and pro-inflammatory cytokines. Accordingly, different strategies have been pursued to develop anti-allergic and anti-inflammatory candidates by regulating the function of mast cells. The purpose of this study was to determine the effectiveness of elaeocarpusin (EL) on mast cell-mediated allergic inflammation. We isolated EL from L. (Elaeocarpaceae), which is known to possess anti-inflammatory properties. For this study, various sources of mast cells and mouse anaphylaxis models were used. EL suppressed the induction of markers for mast cell degranulation, such as histamine and β-hexosaminidase, by reducing intracellular calcium levels. Expression of pro-inflammatory cytokines, such as tumor necrosis factor-α and IL-4, was significantly decreased in activated mast cells by EL. This inhibitory effect was related to inhibition of the phosphorylation of Fyn, Lyn, Syk, and Akt, and the nuclear translocation of nuclear factor-κB. To confirm the effect of EL , immunoglobulin E-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models were induced. EL reduced the PCA reaction in a dose dependent manner. In addition, EL attenuated ASA reactions such as hypothemia, histamine release, and IgE production. Our results suggest that EL is a potential therapeutic candidate for allergic inflammatory diseases that acts via the inhibition of mast cell degranulation and expression of proinflammatory cytokines.
肥大细胞是过敏反应的主要效应细胞,通过释放组胺和促炎细胞因子等炎症介质发挥作用。因此,人们采取了不同的策略,通过调节肥大细胞的功能来开发抗过敏和抗炎候选药物。本研究的目的是确定刺蒴麻酸(EL)对肥大细胞介导的过敏性炎症的有效性。我们从具有抗炎特性的大果杜英(杜英科)中分离出了刺蒴麻酸。在本研究中,使用了多种肥大细胞来源和小鼠过敏反应模型。EL通过降低细胞内钙水平,抑制了肥大细胞脱颗粒标志物如组胺和β-己糖胺酶的诱导。EL使活化肥大细胞中肿瘤坏死因子-α和IL-4等促炎细胞因子的表达显著降低。这种抑制作用与抑制Fyn、Lyn、Syk和Akt的磷酸化以及核因子-κB的核转位有关。为了证实EL的作用,诱导了免疫球蛋白E介导的被动皮肤过敏反应(PCA)和卵清蛋白诱导的主动全身过敏反应(ASA)模型。EL以剂量依赖性方式降低了PCA反应。此外,EL减轻了ASA反应,如体温过低、组胺释放和IgE产生。我们的结果表明,EL是一种潜在的治疗过敏性炎症疾病的候选药物,其作用机制是抑制肥大细胞脱颗粒和促炎细胞因子的表达。