Polydatin inhibits mast cell-mediated allergic inflammation by targeting PI3K/Akt, MAPK, NF-κB and Nrf2/HO-1 pathways.

Polydatin inhibits mast cell-mediated allergic inflammation by targeting PI3K/Akt, MAPK, NF-κB and Nrf2/HO-1 pathways.
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虎杖甙通过靶向 PI3K/Akt、MAPK、NF-kappaB 和 Nrf2/HO-1 通路来抑制肥大细胞介导的过敏性炎症。

DOI:
10.1038/s41598-017-12252-3
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发表时间:
2017-09-19
期刊:
影响因子:
4.6
通讯作者:
Yan G
Yan G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ye J;Piao H;Jiang J;Jin G;Zheng M;Yang J;Jin X;Sun T;Choi YH;Li L;Yan G

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虎杖苷(PD)具有抗过敏性炎症作用,本研究在体内外模型上对其作用机制进行了研究。采用免疫球蛋白介导的被动皮肤过敏反应(PCA)和被动全身过敏反应(PSA)模型证实帕金森病的体内效应。检测肥大细胞内各种信号通路蛋白的表达。适当时采用RT-PCR、ELISA法和Western blotting法。用激酶法测定LYN和FYN两种酶的活性。PD可剂量依赖性地减少PSA模型大鼠伊文思蓝的着色,降低PSA模型大鼠血清组胺浓度,减轻肥大细胞脱颗粒,且不产生细胞毒性。PD可降低促炎细胞因子(肿瘤坏死因子-α、IL-4、IL-1β和IL-8)表达。PD直接抑制Lyn和Syk激酶的活性,下调MAPK、PI3K/AKT和NF-kB等下游信号通路。此外,PD还针对Nrf2/HO-1途径来抑制肥大细胞来源的变态反应性炎症反应。综上所述,这项研究表明帕金森病可能是变态反应性炎症性疾病的候选药物。它直接抑制Lyn和Syk的活性,下调MAPK、PI3K/Akt和NF-κB的信号通路,上调NRF2/HO-1的信号通路,从而抑制肥大细胞脱颗粒。
Polydatin(PD) shows anti-allergic inflammatory effect, and this study investigated its underlying mechanisms in in vitro and in vivo models. IgE-mediated passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA) models were used to confirm PD effect in vivo. Various signaling pathway proteins in mast cell were examined. RT-PCR, ELISA and western blotting were applied when appropriate. Activity of Lyn and Fyn kinases in vitro was measured using the Kinase Enzyme System. PD dose-dependently reduced the pigmentation of Evans blue in the PCA model and decreased the concentration of serum histamine in PSA model, and attenuated the degranulation of mast cells without generating cytotoxicity. PD decreased pro-inflammatory cytokine expression (TNF-α, IL-4, IL-1β, and IL-8). PD directly inhibited activity of Lyn and Syk kinases and down-regulated downstream signaling pathway including MAPK, PI3K/AKT and NF-kB. In addition, PD also targets Nrf2/HO-1 pathway to inhibit mast cell-derived allergic inflammatory reactions. In conclusion, the study demonstrates that PD is a possible therapeutic candidate for allergic inflammatory diseases. It directly inhibited activity of Lyn and Syk kinases and down-regulates the signaling pathway of MAPK, PI3K/AKT and NF-κB, and up-regulates the signaling pathway of Nrf2/HO-1 to inhibit the degranulation of mast cells.
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