Total glucosides of peony improve ovalbumin-induced allergic asthma by inhibiting mast cell degranulation
Total glucosides of peony improve ovalbumin-induced allergic asthma by inhibiting mast cell degranulation
复制标题
牡丹总苷通过抑制肥大细胞脱颗粒改善卵清蛋白诱发的过敏性哮喘
DOI：
10.1016/j.jep.2019.112136
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发表时间：
2019-11-15
影响因子：
5.4
通讯作者：
Fu, Huiying
中科院分区：
文献类型：
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作者：
Shou, Qiyang;Lang, Jiali;Fu, Huiying
民族药理学的相关性：芍药Pall。牡丹是一种药用植物，用于小青龙汤，这是一种治疗哮喘的常用中药。芍药根的主要活性成分-被描述为芍药总苷（TGP）-对内皮细胞具有抗炎，免疫调节和保护作用，并且已知它们可以改善类风湿性关节炎。本研究探讨了白芍总苷（TGP）治疗过敏性哮喘的作用机制。材料与方法：采用卵蛋白（OVA）与氢氧化铝凝胶混合注射和雾化吸入诱发BALB/c小鼠过敏性哮喘。以卵蛋白致敏小鼠为研究对象，通过检测气道高反应性、白细胞分类计数、细胞因子检测及肺组织病理学分析，观察白芍总苷的抗哮喘作用。以β-氨基己糖苷酶活性为生物标志物，评价白芍总苷对肥大细胞脱颗粒的影响。结果：TGP能降低哮喘小鼠气道高反应性，改善肺组织病理，减少炎性细胞浸润和胶原沉积。TGP还显著降低BALF白细胞、嗜酸性粒细胞和中性粒细胞计数，沿着趋化因子和细胞因子，如嗜酸性粒细胞趋化因子、TNF-α、IL-4和MIP-1 α，在OVA攻击小鼠的血清和肺中。这些作用进一步证实了β-氨基己糖苷酶释放的减少和肥大细胞脱颗粒中Ca 2+内流的抑制。结论：我们的研究结果表明，TGP改善OVA诱导的小鼠过敏性哮喘，主要是通过抑制Ca 2+内流依赖性肥大细胞脱颗粒。
Ethnopharmacological relevance: Paeonia lactiflora Pall. (peony) is a medicinal plant used in the Xiaoqinglong decoction, a commonly prescribed traditional Chinese medicine for asthma. The main active ingredients of peony roots-described as the total glucosides of peony (TGP)-have anti-inflammatory, immunomodulatory, and protective effects on endothelial cells, and they are known to improve rheumatoid arthritis. This study explored the underlying mechanism of TGP activity in the treatment of allergic asthma.Materials and methods: Allergic asthma was induced in BALB/c mice by administering injections of ovalbumin (OVA) mixed with aluminum hydroxide gel and inhaling nebulized OVA. The OVA-sensitized mice were treated with TGP by oral gavage, and the potentially anti-asthmatic treatment effect was studied by testing airway hyperresponsiveness, classifying and counting of leukocytes, performing cytokine assays, and analyzing the lung histopathology. The beta-hexosaminidase activity was assayed as a biomarker to evaluate the effect of TGP on mast cell degranulation. The mechanism of TGP was explored by monitoring the Ca2+ influx level in mast cells (RBL-2H3) using a Ca2+ fluorescent probe technique.Results: In mice with OVA-induced allergic asthma, TGP reduced airway hyperresponsiveness and improved lung tissue pathology, which included a decrease in inflammatory cell infiltration and collagen deposition. TGP also significantly lowered BALF leukocyte, eosinophil, and neutrophil counts, along with chemokines and cytokines, such as eotaxin, TNF-alpha, IL-4, and MIP-1 alpha, in serum and lungs of OVA-challenged mice. These effects were further confirmed with the decrease of beta-hexosaminidase release and the inhibition of Ca2+ influx in mast cell degranulation.Conclusions: Our findings suggest that TGP improved OVA-induced allergic asthma in mice mainly by suppressing Ca2+ influx-dependent mast cell degranulation.