欧前胡素对IgE介导的肥大细胞活化的影响
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摘要
目的通过体内及体外实验,初步探究欧前胡素(imperatorin,IMP)在肥大细胞脱颗粒中的作用机制。方法建立大鼠被动皮肤过敏反应(passive cutaneous anaphylaxis,PCA)模型,采用比色测定法检测IMP在体内对肥大细胞的影响;通过体外实验观察欧前胡素在肥大细胞的组胺释放、钙内流、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)释放中的作用,以及对Pi3k/Akt和NF-κB信号通路的影响。结果体内实验结果显示,欧前胡素(15 mg·kg~(-1),30 mg·kg~(-1),60 mg·kg~(-1))明显抑制大鼠过敏反应。体外实验结果表示,欧前胡素(10μmol·L~(-1)、20μmol·L~(-1)、40μmol·L~(-1))显著减少肥大细胞中TNF-α、IL-6的含量以及组胺释放和钙内流,并且抑制NF-κB p65蛋白的表达。结论 IMP的抗过敏作用可能部分是通过抑制Pi3k/Akt和NF-κB信号通路,进而减少肥大细胞释放组胺、钙内流,降低TNF-α、IL-6等炎症因子的水平而实现的。
To investigate the roles of imperatorin(IMP) in mast cell degranulation and its mechanism in vivo and in vitro, colorimetric assay was employed to detect the influence of IMP on the rats of PCA model, we also observed the effects of IMP on histamine release, calcium influx, TNF-α and IL-6 release in mast cells, as well as the effects on Pi3k/Akt and NF-κB signaling pathways. In vivo experimental data showed that IMP(15 mg·kg~(-1),30 mg·kg~(-1), 60 mg·kg~(-1)) significantly inhibited allergic reactions in rats; in vitro data indicated that IMP(10 μmol·L~(-1), 20 μmol·L~(-1), 40 μmol·L~(-1)) significantly reduced TNF-α and IL-6 levels, histamine release and calcium influx of mast cells, and inhibited the expression of NF-κB p65 protein. Taken together, the anti-allergic effect of IMP may be partially achieved by inhibiting the Pi3k/Akt and NF-κB signaling pathways, thereby reducing the histamine and calcium influx from mast cells and reducing the levels of inflammatory factors such as TNF-α, IL-6 and so on.
To investigate the roles of imperatorin(IMP) in mast cell degranulation and its mechanism in vivo and in vitro, colorimetric assay was employed to detect the influence of IMP on the rats of PCA model, we also observed the effects of IMP on histamine release, calcium influx, TNF-α and IL-6 release in mast cells, as well as the effects on Pi3k/Akt and NF-κB signaling pathways. In vivo experimental data showed that IMP(15 mg·kg~(-1),30 mg·kg~(-1), 60 mg·kg~(-1)) significantly inhibited allergic reactions in rats; in vitro data indicated that IMP(10 μmol·L~(-1), 20 μmol·L~(-1), 40 μmol·L~(-1)) significantly reduced TNF-α and IL-6 levels, histamine release and calcium influx of mast cells, and inhibited the expression of NF-κB p65 protein. Taken together, the anti-allergic effect of IMP may be partially achieved by inhibiting the Pi3k/Akt and NF-κB signaling pathways, thereby reducing the histamine and calcium influx from mast cells and reducing the levels of inflammatory factors such as TNF-α, IL-6 and so on.
引文
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[14]赵雨喆,咸哲民,姜京植,等.欧前胡素通过p38MAPK/NF-κB途径改善哮喘小鼠气道炎症[J].免疫学杂志,2018,34(9):737-743.
[2]Thangam EB,Jemima EA,Singh H,et al.The role of histamine and histamine receptors in mast cell-mediated allergy and inflammation:the hunt for new therapeutic targets[J].Front Immunol,2018,9:1873.
[3]Yang WQ,Zhu ZX,Song YL,et al.Dimeric furanocoumarins from the roots of Angelica dahurica[J].Nat Prod Res,2017,31(8):870-877.
[4]Lin CL,Hsiao G,Wang CC,et al.Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells[J].Pharmacol Res,2016,110:111-121.
[5]Wang KS,Lv Y,Wang Z,et al.Imperatorin efficiently blocks TNF-alpha-mediated activation of ROS/PI3K/Akt/NF-kappaB pathway[J].Oncol Rep,2017,37(6):3397-3404.
[6]Endo M,Beppu H,Akiyama H,et al.Agaritine purified from Agaricus blazei Murrill exerts anti-tumor activity against leukemic cells[J].BBA General Subjects,2010,1800(7):669-673.
[7]Choi YH,Yan GH.Anti-allergic effects of scoparone on mast cell-mediated allergy model[J].Phytomedicine,2009,16(12):1089-1094.
[8]Bao Y,Wang S,Gao Y,et al.MicroRNA-126 accelerates IgE-mediated mast cell degranulation associated with the PI3K/Akt signaling pathway by promoting Ca(2+)influx[J].Exp Ther Med,2018,16(3):2763-2769.
[9]Kim HY,Jeong HJ,Kim HM.Anti-allergic and antiinflammatory effects of the Bcl-2 inhibitor ABT-737 on experimental allergic rhinitis models[J].Eur J Pharmacol,2018,833:34-43.
[10]Kraus LF,Scheurmann N,Frenzel DF,et al.9-cisRetinoic acid induces a distinct regulatory dendritic cell phenotype that modulates murine delayed-type allergy[J].Contact Dermatitis,2018,78(1):41-54.
[11]门继光,金哲悟,李建红,等.姬松茸多糖对肥大细胞脱颗粒的影响[J].中药药理与临床,2014,30(3):86-89.
[12]Kobayashi H,Yoshida R,Kanada Y,et al.Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model[J].JCancer Res Clin Oncol,2005,131(8):527-538.
[13]Zegeye MM,Lindkvist M,Falker K,et al.Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells[J].Cell Commun Signal,2018,16(1):55.
[14]赵雨喆,咸哲民,姜京植,等.欧前胡素通过p38MAPK/NF-κB途径改善哮喘小鼠气道炎症[J].免疫学杂志,2018,34(9):737-743.