College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
Biol Pharm Bull. 2012;35(2):216-22. doi: 10.1248/bpb.35.216.
The high-affinity receptor for immunoglobulin E (IgE) (FcεRI)-mediated activation of mast cells plays an important role in various allergic diseases. To assess the anti-allergic activity of natural vanadium-containing Jeju groundwater (JW), an in vivo passive cutaneous anaphylaxis (PCA) animal model and in vitro mouse bone marrow-derived mast cells (BMMCs) was used. JW inhibited cyclooxygenase-2 (COX-2)-dependent prostaglandin D(2) (PGD(2)) generation in a dose-dependent manner, with a concomitant reduction of COX-2 protein expression in IgE-induced BMMCs. In addition, JW inhibited 5-lipoxygenase (5-LOX)-dependent generation of leukotriene C(4) (LTC(4)) as well as degranulation in a dose-dependent manner. These results demonstrate that JW has dual COX-2/5-LOX inhibitory activity. In addition, vanadium pentoxide (V(2)O(5)), which is the major vanadium component of JW, also inhibited PGD(2) and LTC(4) generation as well as degranulation in IgE-induced BMMCs. Furthermore, oral administration of JW dose-dependently inhibited mast cell-dependent passive anaphylactic reaction in IgE-sensitized mice. Taken together, these results suggest that JW may be useful in regulating mast cell-mediated allergic response through the suppression of eicosanoid generation and degranulation in mast cells.
免疫球蛋白 E(IgE)高亲和力受体(FcεRI)介导的肥大细胞激活在各种过敏性疾病中发挥重要作用。为了评估天然含钒济州地下水(JW)的抗过敏活性,使用了体内被动皮肤过敏反应(PCA)动物模型和体外小鼠骨髓来源的肥大细胞(BMMC)。JW 以剂量依赖性方式抑制环氧化酶-2(COX-2)依赖性前列腺素 D2(PGD2)的生成,并伴有 IgE 诱导的 BMMC 中 COX-2 蛋白表达的降低。此外,JW 还以剂量依赖性方式抑制 5-脂氧合酶(5-LOX)依赖性白三烯 C4(LTC4)的生成和脱颗粒。这些结果表明 JW 具有双重 COX-2/5-LOX 抑制活性。此外,JW 的主要钒成分五氧化二钒(V2O5)也抑制 IgE 诱导的 BMMC 中 PGD2 和 LTC4 的生成以及脱颗粒。此外,JW 的口服给药剂量依赖性地抑制了 IgE 致敏小鼠中肥大细胞依赖性被动过敏反应。综上所述,这些结果表明 JW 通过抑制肥大细胞中类花生酸的生成和脱颗粒,可能对调节肥大细胞介导的过敏反应具有重要作用。