关键词: Anti-allergic effect Fucosterol Mouse bone marrow-derived cultured mast cells Passive cutaneous anaphylaxis Sargassum horneri

Mesh : Mice Animals Immunoglobulin E / metabolism Serum Albumin, Bovine Sargassum / metabolism Mast Cells Passive Cutaneous Anaphylaxis Hypersensitivity / drug therapy Tumor Necrosis Factor-alpha / metabolism Anaphylaxis Cell Degranulation Mice, Inbred BALB C Anti-Allergic Agents / pharmacology therapeutic use Stigmasterol / analogs & derivatives

来  源:   DOI:10.1016/j.intimp.2024.111851

Abstract:
Allergic diseases have become a serious problem worldwide and occur when the immune system overreacts to stimuli. Sargassum horneri is an edible marine brown alga with pharmacological relevance in treating various allergy-related conditions. Therefore, this study aimed to investigate the effect of fucosterol (FST) isolated from S. horneri on immunoglobulin E(IgE)/bovine serum albumin (BSA)-stimulated allergic reactions in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice. The in silico analysis results revealed the binding site modulatory potential of FST on the IgE and IgE-FcεRI complex. The findings of the study revealed that FST significantly suppressed the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of β-hexosaminidase and histamine in a dose-dependent manner. In addition, FST effectively decreased the expression of FcεRI on the surface of BMCMCs and its IgE binding. FST dose-dependently downregulated the expression of allergy-related cytokines (interleukin (IL)-4, -5, -6, -13, tumor necrosis factor (TNF)-α, and a chemokine (thymus and activation-regulated chemokine (TARC)) by suppressing the activation of nuclear factor-κB (NF-κB) and Syk-LAT-ERK-Gab2 signaling in IgE/BSA-stimulated BMCMCs. As per the histological analysis results of the in vivo studies with IgE-mediated PCA in BALB/c mice, FST treatment effectively attenuated the PCA reactions. These findings suggest that FST has an immunopharmacological potential as a naturally available bioactive compound for treating allergic reactions.
摘要:
过敏性疾病已成为世界范围内的严重问题,并在免疫系统对刺激反应过度时发生。Sargassumhorneri是一种可食用的海洋褐藻,在治疗各种过敏相关疾病方面具有药理相关性。因此,本研究旨在研究从S.horneri中分离的岩藻甾醇(FST)对小鼠骨髓源性培养的肥大细胞(BMCMC)中免疫球蛋白E(IgE)/牛血清白蛋白(BSA)刺激的过敏反应和BALB/c小鼠被动皮肤过敏反应(PCA)的影响。计算机模拟分析结果揭示了FST在IgE和IgE-FcεRI复合物上的结合位点调节潜力。研究结果表明,FST通过以剂量依赖性方式抑制β-己糖胺酶和组胺的释放,可显着抑制IgE/BSA刺激的BMCMC的脱颗粒。此外,FST有效降低了FcεRI在BMCMC表面的表达及其IgE结合。FST剂量依赖性下调过敏相关细胞因子(白细胞介素(IL)-4,-5,-6,-13,肿瘤坏死因子(TNF)-α,和趋化因子(胸腺和活化调节的趋化因子(TARC)),通过抑制IgE/BSA刺激的BMCMC中核因子κB(NF-κB)和Syk-LAT-ERK-Gab2信号的活化。根据BALB/c小鼠体内IgE介导PCA的组织学分析结果,FST处理有效地减弱了PCA反应。这些发现表明FST具有作为用于治疗变态反应的天然可用的生物活性化合物的免疫药理学潜力。
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