Protostemonine attenuates alternatively activated macrophage and DRA-induced asthmatic inflammation
Protostemonine attenuates alternatively activated macrophage and DRA-induced asthmatic inflammation
复制标题
原百部碱可减轻交替激活的巨噬细胞和 DRA 诱导的哮喘炎症
DOI：
10.1016/j.bcp.2018.07.003
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发表时间：
2018-09-01
影响因子：
5.8
通讯作者：
Qian, Feng
中科院分区：
文献类型：
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作者：
Song, Yunduan;Wu, Yaxian;Qian, Feng
哮喘是最常见的肺部疾病之一，由于缺乏有效的药物，严重威胁着人类的生命。原百部碱（Protostemonine，PSN）是从百部（Stemona sesslifolia）根中提取的一种活性生物碱，对急性肺损伤和急性肝衰竭具有抗炎作用。然而，尚未确定PSN是否减轻哮喘炎症。本研究采用尘螨、豚草、曲霉等致敏小鼠哮喘模型，观察PSN对小鼠肺嗜酸性粒细胞浸润、杯状细胞增生、粘液分泌、IgE和Th 2型细胞因子（IL-4、IL-5、IL-13和IL-33）产生的抑制作用。此外，PSN还减弱了肺组织中精氨酸酶-1（Arg-1）、Ym-1和Fizz-1（AAM（交替激活的巨噬细胞）极化的标志物）的表达。此外，PSN减弱了IL-4诱导的骨髓源性巨噬细胞（BMDM）中Arg-1、Ym-1和Fizz-1的表达。PSN处理降低BMDM中IL-4诱导的STAT 6磷酸化、KLF 4和IRF 4表达。总之，我们的研究结果表明，PSN改善AAM极化和哮喘炎症，可能是一种潜在的治疗哮喘的药物。
Asthma is one of the most common pulmonary diseases that threatens human life because of lack of effective medicines. Protostemonine (PSN), an active alkaloid extracted from the roots of Stemona sesslifolia, has anti-inflammatory effects on acute lung injury and acute liver failure. However, it has not been defined whether PSN alleviates asthmatic inflammation. Here, we reported that PSN inhibits pulmonary eosinophil infiltration, goblet cell hyperplasia, mucus secretion, IgE and Th2 cytokine (IL-4, IL-5, IL-13 and IL-33) production by using DRA (dust mites, ragweed and aspergillus)-induced murine asthma model. Moreover, PSN also attenuated the expression of Arginase-1 (Arg-1), Ym-1 and Fizz-1, markers of AAM (alternatively activated macrophage) polarization, in lung tissues. In addition, PSN attenuated IL-4-induced expression of Arg-1, Ym-1 and Fizz-1 in bone marrow derived macrophages (BMDMs). Treatment with PSN decreased IL-4-induced STAT6 phosphorylation, KLF4 and IRF4 expression in BMDMs. Collectively, our results indicated that PSN ameliorates AAM polarization and asthmatic inflammation and might be a potential agent for treating asthma.