Mast cells are important effector cells in immunoglobulin (Ig) E-mediated allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid, a natural product, has shown anti-oxidant and anti-inflammatory activities. In the present study, we investigated the anti-allergic inflammatory effects of ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models, oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic reactions such as hypothermia, histamine release, IgE production and vasodilation; administration of o-VA also suppressed the mast cell degranulator compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1-100 μmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells by decreasing the intracellular free calcium level, and suppressed the expression of pro-inflammatory cytokines TNF-α and IL-4. Pretreatment of RBL-2H3 cells with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the nuclear translocation of nuclear factor-κB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (FcεRI) on the surface of mast cells.

中文翻译：

---

2-羟基-3-甲氧基苯甲酸可通过调节FcεRI信号通路减弱小鼠肥大细胞介导的过敏反应。

肥大细胞是免疫球蛋白（Ig）E介导的过敏反应（例如哮喘，特应性皮炎和鼻炎）中的重要效应细胞。天然产物香草酸已显示出抗氧化剂和消炎活性。在本研究中，我们研究了原香草酸（2-羟基-3-甲氧基苯甲酸，o-VA）的抗过敏炎症作用，原香草酸是从砂仁黄砂中分离出的香草酸的衍生物。在小鼠过敏反应模型中，口服口服o-VA（2、10、50 mg / kg）剂量依赖性地减轻卵清蛋白诱导的主动系统性过敏反应和IgE介导的皮肤过敏反应，例如体温过低，组胺释放，IgE产生和血管舒张；o-VA的给药也抑制了肥大细胞脱粒剂化合物48/80引起的过敏反应。在体外培养的肥大细胞系RBL-2H3和分离的大鼠腹膜肥大细胞中，o-VA（1-100μmol/ L）预处理可通过降低细胞内游离钙水平剂量依赖性抑制DNP-HSA诱导的肥大细胞脱粒并抑制促炎细胞因子TNF-α和IL-4的表达。用o-VA预处理RBL-2H3细胞可抑制DNP-HSA诱导的Lyn，Syk，Akt磷酸化以及核因子-κB的核易位。总之，o-VA通过阻断肥大细胞表面高亲和力IgE受体（FcεRI）下游的信号传导途径来抑制肥大细胞介导的过敏性炎症反应。o-VA（1-100μmol/ L）预处理通过降低细胞内游离钙水平，剂量依赖性地抑制DNP-HSA诱导的肥大细胞脱粒，并抑制促炎细胞因子TNF-α和IL-4的表达。用o-VA预处理RBL-2H3细胞可抑制DNP-HSA诱导的Lyn，Syk，Akt磷酸化以及核因子-κB的核易位。总之，o-VA通过阻断肥大细胞表面高亲和力IgE受体（FcεRI）下游的信号传导途径来抑制肥大细胞介导的过敏性炎症反应。o-VA（1-100μmol/ L）预处理通过降低细胞内游离钙水平，剂量依赖性地抑制DNP-HSA诱导的肥大细胞脱粒，并抑制促炎细胞因子TNF-α和IL-4的表达。用o-VA预处理RBL-2H3细胞可抑制DNP-HSA诱导的Lyn，Syk，Akt磷酸化以及核因子-κB的核易位。总之，o-VA通过阻断肥大细胞表面高亲和力IgE受体（FcεRI）下游的信号传导途径来抑制肥大细胞介导的过敏性炎症反应。