Synergistic inhibitory effects of naproxen in combination with magnolol on TPA-induced skin inflammation in mice

Synergistic inhibitory effects of naproxen in combination with magnolol on TPA-induced skin inflammation in mice
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萘普生联合厚朴酚对 TPA 诱导的小鼠皮肤炎症的协同抑制作用

DOI:
10.1039/c6ra03926j
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发表时间:
2016-01-01
期刊:
影响因子:
3.9
通讯作者:
Du, Zhiyun
Du, Zhiyun
中科院分区:
化学3区
文献类型:
--
作者:
Yue, Yuan;Liu, Wenfeng;Du, Zhiyun

文献摘要

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萘普生与具有一系列药理作用的草药的组合是改善其生物活性并限制其不良反应的潜在替代方案。受厚朴酚(一种在厚朴树皮中发现的活性成分)的启发,我们因此评估了萘普生(N)加厚朴酚(M)在12-O-十四酰基佛波醇-13-乙酸酯(TPA)诱导的皮肤炎症中的疗效。在施用期间,用N和M处理显著减少皮肤炎症,并且N和M的组合产生协同效应。进一步的机制研究清楚地表明,A3(N:M = 1:3,mol mol−1)显著抑制TPA诱导的促炎细胞因子和考克斯-2表达,抑制NF-κB活性,下调IκBα和IκB激酶(IKK)活性,并抑制PI 3 K/Akt和PI 3 K/PKC信号通路。    上述结果表明,N和M联合应用可通过阻断PI 3 K/Akt/IKK和PI 3 K/PKC/IKK信号通路有效抑制TPA诱导的皮肤炎症反应。
The combination of naproxen with herbs having a range of pharmacological effects is a potential alternative to improve their bioactivity and limit their adverse effects. Inspired by magnolol, an active constituent found in the bark of Magnolia officinalis, we therefore evaluated the efficacy of naproxen (N) plus magnolol (M) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation. During application, treatment with N and M significantly reduced skin inflammation, and the combination of N and M resulted in a synergistic effect. Further mechanistic investigations clearly demonstrated that A3 (N : M = 1 : 3, mol mol−1) markedly suppressed TPA-induced pro-inflammatory cytokines and COX-2 expressions, inhibited NF-κB activity, downregulated IκBα and IκB kinase (IKK) activities, and inhibited PI3K/Akt and PI3K/PKC signaling pathways. These results indicated that a combination of N and M effectively inhibited TPA-induced skin inflammation via blocking PI3K/Akt/IKK and PI3K/PKC/IKK signaling pathways.