College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
Center for Translational Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Toxicol Appl Pharmacol. 2019 Mar 1;366:46-53. doi: 10.1016/j.taap.2019.01.019. Epub 2019 Jan 23.
The classical mast cells degranulation pathway is mediated by FcεRI aggregation and varies in strength among subjects. Dehydroandrographolide (DA) is one of principal components of Andrographis paniculata (Burm.f.) Nees (family: Acanthaceae) and considered the main contributors of its therapeutic properties, such as anti-tumor. In this study, inhibition of IgE-mediated anaphylactic reactions and anti-inflammatory potential of DA were investigated. The anti-anaphylactic activity of DA was investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. The release of cytokines was measured using ELISA kits. Human Phospho-Kinase Array kit and western blotting were used to explore the related molecular signaling pathways. DA inhibited IgE-mediated mast cell activation, including degranulation and release of cytokines in vitro. Moreover, DA reduced the degree of swelling and Evans blue exudation of mice paw in a dose-dependent manner by inhibiting mast cell degranulation. DA obviously reduced the concentrations of histamine, TNF-α, MCP-1, IL-8, IL-13, and IL-4 in mice serum and inhibited IgE-mediated anaphylactic reactions as a potential P-PLCγ inhibitor. Our study reveals that DA can inhibit allergic responses in vivo and in vitro, and it may be regarded as a novel P-PLCγ inhibitor for preventing mast cell-immediate and delayed allergic diseases.
经典的肥大细胞脱颗粒途径是由 FcεRI 聚集介导的,在不同个体之间存在强度差异。去氢穿心莲内酯(DA)是穿心莲(Burm.f.) Nees(爵床科)的主要成分之一,被认为是其治疗特性的主要贡献者,如抗肿瘤。在这项研究中,研究了 DA 抑制 IgE 介导的过敏反应和抗炎潜力。通过体内皮肤肿胀和渗出试验以及体外肥大细胞脱颗粒试验研究了 DA 的抗过敏活性。使用 ELISA 试剂盒测量细胞因子的释放。使用人磷酸激酶阵列试剂盒和 Western blot 探索相关的分子信号通路。DA 抑制 IgE 介导的肥大细胞活化,包括体外脱颗粒和细胞因子释放。此外,DA 通过抑制肥大细胞脱颗粒,以剂量依赖的方式降低小鼠爪肿胀和 Evans 蓝渗出的程度。DA 明显降低了小鼠血清中组胺、TNF-α、MCP-1、IL-8、IL-13 和 IL-4 的浓度,并作为潜在的 P-PLCγ 抑制剂抑制 IgE 介导的过敏反应。我们的研究表明,DA 可以抑制体内和体外的过敏反应,它可能被视为预防肥大细胞即刻和迟发性过敏疾病的新型 P-PLCγ 抑制剂。