Isoforskolin Alleviates AECOPD by Improving Pulmonary Function and Attenuating Inflammation Which Involves Downregulation of Th17/IL-17A and NF-κB/NLRP3.
Isoforskolin Alleviates AECOPD by Improving Pulmonary Function and Attenuating Inflammation Which Involves Downregulation of Th17/IL-17A and NF-κB/NLRP3.
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异福司可林通过改善肺功能和减轻炎症来缓解 AECOPD，炎症涉及 Th17/IL-17A 和 NF-kappa B/NLRP3 的下调
DOI：
10.3389/fphar.2021.721273
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发表时间：
2021
影响因子：
5.6
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Xiao C;Cheng S;Li R;Wang Y;Zeng D;Jiang H;Liang Y;Huang R;Pan H;Wu X;Fang Y;Chen C;Li X;Zhang R;Wang X;Yang Z;Yang W
慢性阻塞性肺疾病(COPD)是世界范围内发病率和死亡率的主要原因，被广泛认为与吸烟(CS)有关，而病毒感染会引发COPD的急性加重(AECOPD)。异佛尔斯柯林(Isoforskolin，ISOF)是产于云南中国的一种植物油茶的生物活性成分。在急性肺损伤动物模型上，已证实异黄连具有抗炎作用。在本研究中，我们探讨了ISOF预防和治疗AECOPD的疗效和机制。将小鼠暴露在CS中18周，然后感染A/波多黎各/8/34(H1N1)流感病毒。染毒8周后，当模型小鼠体重和肺功能明显下降时，给予ISOF(0.5，2 mg/kg)灌胃，1次/d。观察肺组织中病毒载量、肺功能、肺组织形态、Th17细胞和炎症细胞因子的变化。检测核因子κB(NF-κB)和NOD样受体吡咯环蛋白3(NLRP3)在炎症体通路中的表达。结果表明，ISOF治疗可降低模型小鼠肺组织匀浆中病毒载量，降低肺指数，减轻肺组织病理损伤。改善肺功能，增加FEV0.1/FVC，降低Rn和RRS。治疗后肺组织匀浆中炎性介质(肿瘤坏死因子-α、IL-1β、IL-6、IL-17A、单核细胞趋化蛋白-1、免疫球蛋白、IP-10、C反应蛋白)水平明显降低。流式细胞仪检测显示，异烟肼可降低肺组织中Th1 7细胞的比例，降低肺组织中RoRγt和p-STAT3的蛋白表达水平。此外，异烟肼还能显著抑制模型小鼠肺组织中NF-κB信号和NLRP3炎性小体的激活。结论：异烟肼通过下调促炎症细胞因子Th17/IL-17A和NF-κB/NLRP3途径，改善肺功能，减轻炎症反应，从而减轻AECOPD。
Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide, is widely considered to be related to cigarette smoke (CS), and viral infections trigger acute exacerbation of COPD (AECOPD). Isoforskolin (ISOF) is a bioactive component from the plant Coleus forskohlii, native to Yunnan in China. It has been demonstrated that ISOF has anti-inflammatory effect on acute lung injury animal models. In the present study, we investigated the efficacy and mechanism of ISOF for the prevention and treatment of AECOPD. Mice were exposed to CS for 18 weeks and then infected with influenza virus A/Puerto Rico/8/34 (H1N1). ISOF (0.5, 2 mg/kg) was intragastrically administered once a day after 8 weeks of exposure to cigarette smoke when the body weight and lung function of model mice declined significantly. The viral load, pulmonary function, lung morphology, Th17 cells, and inflammatory cytokines in lung tissues were evaluated. The expression of nuclear factor κB (NF-κB) and NOD-like receptor pyrin domain–containing protein 3 (NLRP3) inflammasome pathways were detected. The results showed that ISOF treatment reduced the viral load in the lung homogenate, decreased the lung index of model mice, and lung pathological injuries were alleviated. ISOF also improved the pulmonary function with increased FEV0.1/FVC and decreased Rn and Rrs. The levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17A, MCP-1, MIG, IP-10, and CRP) in the lung homogenate were reduced after ISOF treatment. ISOF decreased the proportion of Th17 cells in the lung tissues by the flow cytometry test, and the protein expression levels of RORγt and p-STAT3 were also decreased. Furthermore, ISOF significantly inhibited the activation of NF-κB signaling and NLRP3 inflammasome in the lung tissues of model mice. In conclusion, ISOF alleviates AECOPD by improving pulmonary function and attenuating inflammation via the downregulation of proinflammatory cytokines, Th17/IL-17 A, and NF-κB/NLRP3 pathways.
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影响因子：
5.9
作者：
Brown, Stacey-Ann Whittaker;Braman, Sidney
通讯作者：
Braman, Sidney
影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
DOI：
10.1038/nrd4228
发表时间：
2014-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Ghorani V;Boskabady MH;Khazdair MR;Kianmeher M
通讯作者：
Kianmeher M
影响因子：
10
作者：
Kim, Richard Y.;Pinkerton, James W.;Hansbro, Philip M.
通讯作者：
Hansbro, Philip M.