Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China.
College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China.
Int Immunopharmacol. 2020 Dec;89(Pt A):107073. doi: 10.1016/j.intimp.2020.107073. Epub 2020 Oct 8.
Allergic asthma is the most common type of asthma which characterized by inflammatory responses of the airways. Alpinetin, a flavonoid compound derived from the ginger family of medicinal herbs, possesses various biological properties including anti-inflammatory, anti-oxidant and other medical effects. In this study, we aimed to evaluate the effects of alpinetin on OVA-induced allergic asthma, and further to examine its molecular mechanisms underlying these processes in vivo and in vitro. Mice were sensitized and challenged with OVA to build allergic asthma model in vivo. Bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells analysis and lung tissues were examined for histopathological examination. The levels of IL-5, IL-13, IL-4, IgE, TNF-α, IL-6 and IL-1β were determined by the respective ELISA kits. The PI3K/AKT/NF-κB and HO-1 signaling pathways were examined by western blot analysis. The results showed that alpinetin significantly ameliorated OVA-induced pathologic changes of lungs, such as decreasing massive inflammatory cell infiltration and mucus hypersecretion, and reduced the number of inflammatory cells in BALF. Alpinetin also decreased the OVA-induced levels of IL-4, IL-5, IL-13 and IgE. Furthermore, alpinetin inhibited OVA-induced phosphorylation of p65, IκB, PI3K and AKT, and the activity of HO-1 in vivo. More importantly, these anti-inflammatory effects and molecular mechanisms of alpinetin has also been confirmed in LPS-stimulated RAW 264.7 macrophages in vitro. In conclusion, above results indicate that alpinetin exhibites a potent anti-inflammatory activity in allergic asthma through modulating PI3K/AKT/NF-κB and HO-1 signaling pathways, which would be used as a promising therapy agent for allergic asthma.
过敏性哮喘是最常见的哮喘类型，其特征是气道的炎症反应。白杨素是一种源自姜科药用植物的黄酮类化合物，具有多种生物特性，包括抗炎、抗氧化等医疗作用。在这项研究中，我们旨在评估白杨素对 OVA 诱导的过敏性哮喘的影响，并进一步研究其在体内和体外的作用机制。通过用 OVA 致敏和激发来构建体内过敏性哮喘模型，然后收集支气管肺泡灌洗液（BALF）进行炎症细胞分析，并检查肺组织进行组织病理学检查。通过各自的 ELISA 试剂盒测定 IL-5、IL-13、IL-4、IgE、TNF-α、IL-6 和 IL-1β 的水平。通过 Western blot 分析检测 PI3K/AKT/NF-κB 和 HO-1 信号通路。结果表明，白杨素显著改善了 OVA 诱导的肺部病理变化，如减少大量炎症细胞浸润和黏液分泌过度，并减少 BALF 中的炎症细胞数量。白杨素还降低了 OVA 诱导的 IL-4、IL-5、IL-13 和 IgE 水平。此外，白杨素抑制了 OVA 诱导的 p65、IκB、PI3K 和 AKT 磷酸化，以及 HO-1 在体内的活性。更重要的是，这些抗炎作用和白杨素的分子机制在 LPS 刺激的 RAW 264.7 巨噬细胞中也得到了证实。综上所述，这些结果表明，白杨素通过调节 PI3K/AKT/NF-κB 和 HO-1 信号通路，在过敏性哮喘中表现出强大的抗炎活性，可作为治疗过敏性哮喘的有前途的治疗剂。
