背景:齐墩果酸(OA)是在多种草药和植物中发现的活性化合物。虽然OA已被广泛归因于多种生物活性,专注于其抗过敏炎症特性的研究不足。
目的:鉴于过敏性疾病的迅速增加和缺乏基本的治疗选择,本研究旨在寻找一种安全有效的治疗过敏性疾病的方法。
方法:我们使用佛波醇-12-肉豆蔻酸酯13-乙酸酯加钙离子载体A23187(PMACI)刺激的人肥大细胞(HMC)-1,和化合物48/80诱导的过敏性休克的小鼠模型,评估了OA对过敏性炎症反应的抑制作用和潜在机制。
结果:OA通过抑制Akt的激活抑制了PMACI诱导的HMC-1细胞中促炎细胞因子的表达,p38丝裂原活化蛋白激酶(MAPK),核因子-κB(NF-κB),和信号转导和转录激活因子(STAT)1信号通路。此外,OA通过调节NF-κB和STAT1活化抑制组胺释放和免疫球蛋白E水平,显示出对化合物48/80诱导的过敏性休克的保护作用。
结论:结果显示OA通过转录调控抑制肥大细胞介导的变态反应。我们建议OA对过敏性炎性疾病有潜在的作用,包括过敏反应,并且可能是过敏性疾病的有用治疗剂。
BACKGROUND: Oleanolic acid (OA) is an active compound found in a variety of medicinal herbs and plants. Though OA has been widely attributed with a variety of biological activities, studies focused on its anti-allergic inflammation properties are insufficient.
OBJECTIVE: Given the rapid increase in allergic diseases and the lack of fundamental treatment options, this study aimed to find a safe and effective therapy for allergic disorders.
METHODS: We evaluated the inhibitory effect of OA on allergic inflammatory response and the possible mechanisms underlying the effect using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cell (HMC)-1, and a mouse model of compound 48/80-induced anaphylactic shock.
RESULTS: OA suppressed pro-inflammatory cytokine expressions in PMACI-induced HMC-1 cells by inhibiting activation of the Akt, p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and signal transducer and activator of transcription (STAT) 1 signaling pathways. Moreover, OA showed a protective effect against compound 48/80-induced anaphylactic shock through inhibition of histamine release and immunoglobulin E level via regulation of NF-κB and STAT1 activation.
CONCLUSIONS: The results showed that OA suppressed mast cell-mediated allergic response by transcriptional regulation. We suggest that OA has potential effect against allergic inflammatory disorders, including anaphylaxis, and might be a useful therapeutic agent for allergic disease.