Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
Hefei Yigong Medicine Co., Ltd, Hefei 230088, Anhui, China.
Eur J Pharmacol. 2015 May 5;754:1-10. doi: 10.1016/j.ejphar.2015.02.016. Epub 2015 Feb 19.
The present study, demonstrates that, desloratadine citrate disodium injection (DLC) possesses antihistaminic, anti-allergic and anti-inflammatory properties and elucidates its molecular mechanisms of anti-inflammatory properties. In vitro antihistamine activity of DLC was determined in guinea pig isolated tissues. In vivo antihistamine effects were evaluated after following intravenous administration of DLC in mice with histamine- induced paw edema and in rats with increased capillary permeability. Anti-allergic effects were assessed through passive cutaneous anaphylactic (PCA) reactions in sensitized rodents and ovalbumin-induced allergic rhinitis in rats. Anti-inflammatory properties and molecular mechanisms of DLC were determined on histamine- and lipopolysaccharide (LPS)-induced EA.hy926 endothelial cells. DLC exhibited significant and reversible inhibition of histamine-induced contractions of isolated guinea pig ileum with pA2 value of 8.88. Histamine-induced paw edema and increased capillary permeability were notably inhibited by DLC intravenous administration. In the model of PCA reactions, DLC showed significant activity in a dose-dependent nd potently inhibited both the early-phase and late-phase allergic reaction of ovalbumin-induced allergic rhinitis in rats. DLC alleviated the rhinitis symptoms and inhibited inflammatory cell infiltration, IL-4 and protein leakage in nasal lavage fluid (NLF). In EA.hy926 cells, DLC significantly inhibited the histamine- and LPS- induced IL-6 and IL-8 production and P-selectin and intercellular cell adhesion molecule-1 (ICAM-1) expression. Moreover, DLC reduced translocation of nuclear factor-kappaB (NF-κB) to the nucleus in activated EA.hy926 cells. These results provide evidence that DLC possesses potent antihistaminic, anti-allergic and, anti-inflammatory properties via suppressing IL-6, IL-8, P-selectin and ICAM-1 expression.
本研究表明，枸地氯雷他定二钠注射液（DLC）具有抗组胺、抗过敏和抗炎特性，并阐明了其抗炎特性的分子机制。在豚鼠离体组织中测定 DLC 的体外抗组胺活性。在组胺诱导的爪肿胀和增加的毛细血管通透性的小鼠以及大鼠中，静脉给予 DLC 后评估其体内抗组胺作用。通过致敏啮齿动物的被动皮肤过敏（PCA）反应和卵白蛋白诱导的大鼠过敏性鼻炎评估抗过敏作用。在组胺和脂多糖（LPS）诱导的 EA.hy926 内皮细胞中确定 DLC 的抗炎特性和分子机制。DLC 对分离的豚鼠回肠的组胺诱导收缩具有显著且可逆的抑制作用，pA2 值为 8.88。静脉给予 DLC 可显著抑制组胺诱导的爪肿胀和增加的毛细血管通透性。在 PCA 反应模型中，DLC 呈剂量依赖性显著活性，可显著抑制卵白蛋白诱导的大鼠过敏性鼻炎的早相和晚相过敏反应。DLC 缓解了鼻炎症状并抑制了鼻灌洗液（NLF）中的炎症细胞浸润、IL-4 和蛋白漏出。在 EA.hy926 细胞中，DLC 显著抑制组胺和 LPS 诱导的 IL-6 和 IL-8 产生以及 P-选择素和细胞间黏附分子-1（ICAM-1）的表达。此外，DLC 减少了活化的 EA.hy926 细胞中核因子-κB（NF-κB）向细胞核的易位。这些结果表明，DLC 通过抑制 IL-6、IL-8、P-选择素和 ICAM-1 的表达，具有强大的抗组胺、抗过敏和抗炎特性。
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