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黄花夹竹桃苷 B4 通过抑制 PLC/IP3 和 JAK/STAT3 通路来防止 IgE 依赖性过敏反应。

Anemoside B4 protects against IgE-dependent allergic responses by suppressing the PLC/IP3 and JAK/STAT3 pathways.

机构信息

Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

出版信息

Chem Biol Interact. 2022 Oct 1;366:110153. doi: 10.1016/j.cbi.2022.110153. Epub 2022 Sep 6.

DOI:10.1016/j.cbi.2022.110153
PMID:36084722
Abstract

Anemoside B4 (AB4) is a natural triterpenoid abundant in the roots of Pulsatilla chinensis. Although various biological activities have been widely attributed to AB4, few studies have focused on its antiallergic effects. In this study the inhibitory effects of AB4 on immunoglobulin E (IgE)-mediated allergic responses were investigated, both in vitro and in vivo, and the mechanism of its effects. IgE-mediated passive cutaneous anaphylaxis was used to elucidate the antiallergic effects of AB4 in vivo. The degranulation assay, calcium imaging, and cytokine and chemokine release in the laboratory of allergic disease 2 (LAD2) cell line were used to evaluate the antiallergic effect of AB4 in vitro. Pathological staining was performed to analyze angiectasis. Western blot analysis was performed to investigate the downstream signaling pathways. AB4 dose-dependently attenuated ovalbumin/IgE-induced paw swelling in mice, and reduced the serum concentrations of tumor necrosis factor-alpha and C-C motif chemokine 2. In addition, AB4 suppressed IgE-mediated LAD2 cell degranulation, calcium influx, and PLC/IP3 and JAK/STAT3 phosphorylation. Our results suggest that AB4 inhibits allergic reactions through the PLC/IP3 and JAK/STAT3 pathways.

摘要

白头翁皂苷 B4 (AB4) 是一种天然的三萜皂苷,在白头翁的根部含量丰富。尽管 AB4 具有多种生物活性,但很少有研究关注其抗过敏作用。本研究从体外和体内水平研究了 AB4 对免疫球蛋白 E (IgE) 介导的过敏反应的抑制作用,并探讨了其作用机制。采用 IgE 介导的被动皮肤过敏反应来阐明 AB4 在体内的抗过敏作用。脱颗粒测定、钙成像以及过敏性疾病 2 (LAD2) 细胞系中细胞因子和趋化因子的释放用于评估 AB4 的体外抗过敏作用。进行病理染色以分析血管扩张。采用 Western blot 分析来研究下游信号通路。AB4 呈剂量依赖性抑制卵清蛋白/IgE 诱导的小鼠爪肿胀,并降低肿瘤坏死因子-α和 C-C 基序趋化因子 2 的血清浓度。此外,AB4 抑制 IgE 介导的 LAD2 细胞脱颗粒、钙内流以及 PLC/IP3 和 JAK/STAT3 磷酸化。我们的结果表明,AB4 通过 PLC/IP3 和 JAK/STAT3 通路抑制过敏反应。

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