Dhakal Hima, Kim Min-Jong, Lee Soyoung, Choi Young-Ae, Kim Namkyung, Kwon Taeg Kyu, Khang Dongwoo, Kim Sang-Hyun
Cell & Matrix Research Institute, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Immunoregulatory Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Republic of Korea.
Int Immunopharmacol. 2021 Oct;99:107994. doi: 10.1016/j.intimp.2021.107994. Epub 2021 Aug 13.
Mast cells are the primary cells that play a crucial role in the allergic diseases via secretion of diverse allergic mediators. Ursolic acid (UA) is a naturally occurring anti-inflammatory triterpenoid possessing various biological properties such as immune regulation, antioxidant, and anti-fibrotic. The aim of this study was to evaluate the effects of UA in FcεRI-mediated mast cell activation and allergic inflammation.
In this study, mast cells were stimulated with immunoglobulin E (IgE) and the anti-allergic effects of UA were assessed by measuring the levels of allergic mediators. In vivo effects of UA were observed by generating passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mouse model.
We found that UA inhibited the degranulation of mast cell by suppressing the intracellular calcium level in a concentration-dependent manner. UA inhibited the expression and the release of pro-inflammatory cytokines in mast cells. Anti-allergic effects of UA were demonstrated via suppression of FcεRI-mediated signaling molecules. In addition, UA inhibited the IgE-mediated PCA and ovalbumin-induced ASA reactions in a dose-dependent manner.
Based on these findings, we suggest that UA might have potential as a therapeutic candidate for the treatment of allergic inflammatory diseases via inhibition of FcεRI-mediated mast cell activation.
肥大细胞是通过分泌多种过敏介质在过敏性疾病中起关键作用的主要细胞。熊果酸(UA)是一种天然存在的具有免疫调节、抗氧化和抗纤维化等多种生物学特性的抗炎三萜类化合物。本研究的目的是评估UA对FcεRI介导的肥大细胞活化和过敏性炎症的影响。
在本研究中,用免疫球蛋白E(IgE)刺激肥大细胞,并通过测量过敏介质水平评估UA的抗过敏作用。通过在小鼠模型中产生被动皮肤过敏反应(PCA)和主动全身过敏反应(ASA)观察UA的体内作用。
我们发现UA通过以浓度依赖的方式抑制细胞内钙水平来抑制肥大细胞的脱颗粒。UA抑制肥大细胞中促炎细胞因子的表达和释放。通过抑制FcεRI介导的信号分子证明了UA的抗过敏作用。此外,UA以剂量依赖的方式抑制IgE介导的PCA和卵清蛋白诱导的ASA反应。
基于这些发现,我们认为UA可能通过抑制FcεRI介导的肥大细胞活化而具有作为治疗过敏性炎症疾病的候选药物的潜力。