Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO-1 pathways.
Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO-1 pathways.
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紫檀芪通过 AMPK/Sirt1 和 Nrf2/HO-1 途径抑制氧化应激和过敏性气道炎症
DOI：
10.1002/iid3.490
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Yan G
中科院分区：
文献类型：
--
作者：
Xu C;Song Y;Wang Z;Jiang J;Piao Y;Li L;Jin S;Li L;Zhu L;Yan G
紫檀芪（Pts）可用于过敏性哮喘治疗。AMPK/Sirt1和Nrf2/HO‐1通路是哮喘治疗的潜在靶点。然而，哮喘患者的Pts与AMPK/Sirt1和Nrf2/HO‐1通路之间的关系尚不清楚。在此，我们旨在探讨Pts对氧化应激和过敏性炎症反应的药理作用，以及AMPK/Sirt1和Nrf2/HO‐1通路的作用机制。用卵清蛋白（OVA）建立小鼠哮喘模型。给模型小鼠注射不同浓度的Pts。组织染色观察肺组织病理改变。在体外，用Pts处理脂多糖（LPS）刺激的16HBE细胞。在16HBE细胞中也进行了siAMPKα2、siSirt1和siNrf2的敲除，并用化合物C、EX‐527或ML385处理。采用酶联免疫吸附法检测白细胞介素4 （IL‐4）、IL‐13、IL‐5、总免疫球蛋白E （IgE）和卵细胞特异性免疫球蛋白E（卵细胞特异性免疫球蛋白E）和干扰素γ （IFN‐γ）。气道造影检测气道高反应性（AHR）。同时检测超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和丙二醛（MDA）水平。采用免疫组织化学、免疫印迹和免疫荧光法检测蛋白水平。Pts可显著减轻肺部炎症细胞浸润和杯状细胞增殖。同时，Pts治疗可降低哮喘模型小鼠IL - 4、IL - 13、IL - 5和IgE（总水平和特异水平）。然而，支气管肺泡灌洗液中的IFN‐γ升高。此外，Pts降低了AHR。我们还发现，Pts治疗提高了血清SOD和CAT，降低了MDA。体外实验结果显示，Pts治疗可促进16HBE细胞iNOS、TNF‐α、COX‐2、IL‐1β和IL‐6的表达，延长细胞周期的G0/G1期，缩短G2M期。此外，我们发现Pts促进了16HBE中AMPK的磷酸化，同时抑制了LPS诱导的ROS的增加。此外，Pts治疗抑制了p - AMPK、Sirt1、Nrf2和HO‐1，这反过来导致AMPK/Sirt1和Nrf2/HO‐1通路的缓解。Pts通过调节AMPK/ sirt1和Nrf2/HO‐1信号通路减轻氧化应激和过敏性气道炎症。Pts可以通过AMPK/Sirt1和Nrf2/HO‐1信号通路抑制氧化应激，从而缓解哮喘。因此，Pts可能是治疗哮喘的潜在抗炎药物。
Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO‐1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO‐1 pathways in asthma is unclear. Herein, we aim to explore the pharmacological effects of Pts on oxidative stress and allergic inflammatory response as well as the mechanism involving AMPK/Sirt1 and Nrf2/HO‐1 pathways. Asthma model was established in mice with ovalbumin (OVA). The model mice were treated by different concentrations of Pts. Lung pathological changes were observed through histological staining. In vitro, lipopolysaccharide (LPS)‐stimulated 16HBE cells were treated with Pts. The siAMPKα2, siSirt1 and siNrf2 knockdown, and treatment with compound C, EX‐527 or ML385 were also performed in 16HBE cells. Enzyme‐linked immunosorbent assay was used to detect interleukin‐4 (IL‐4), IL‐13, IL‐5, total and OVA specific immunoglobulin E (IgE), and interferon γ (IFN‐γ). Pneumonography was used to measure the airway hyperreactivity (AHR). Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were also detected. Immunohistochemistry, Western blot and immunofluorescence were used to measure protein levels. Pts significantly attenuated lung inflammatory cell infiltration and goblet cell proliferation. Meanwhile, Pts treatment could reduce IL‐4, IL‐13, IL‐5, and IgE (total and OVA specific) levels in the asthma model mice. However, IFN‐γ in bronchoalveolar lavage fluid was elevated. In addition, Pts reduced AHR. We also found that Pts treatment promoted serum SOD and CAT, and reduced MDA. In vitro results showed that Pts treatment promoted iNOS, TNF‐α, COX‐2, IL‐1β, and IL‐6 expressions in 16HBE cells, prolonged G0/G1 phase of the cell cycle, and resulted in a shortened G2M phase. Moreover, we found that Pts promoted the phosphorylation of AMPK in 16HBE, and meanwhile inhibited the increase of ROS induced by LPS. Additionally, Pts treatment inhibited p‐AMPK, Sirt1, Nrf2 and HO‐1, which in turn leads to the alleviation of AMPK/Sirt1 and Nrf2/HO‐1 pathways. Pts alleviated oxidative stress and allergic airway inflammation via regulation of AMPK/Sirt1and Nrf2/HO‐1 signaling pathways. Pts can relieve asthma by suppressing oxidative stress through the AMPK/Sirt1 and Nrf2/HO‐1 signaling pathways. Thus, Pts might be a potential anti‐inflammatory drug for the treatment of asthma.
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影响因子：
5.6
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1007/s00018-016-2223-0
发表时间：
2016-09
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
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作者：
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作者：
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通讯作者：
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作者：
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通讯作者：
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