Department of Geriatric Respiratory and Critical Care, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Key Laboratory of Respiratory Disease Research and Medical Transformation of Anhui Province, Hefei, China.
Phytother Res. 2021 Jun;35(6):3298-3309. doi: 10.1002/ptr.7051. Epub 2021 Feb 11.
Abscisic acid (ABA), a well-known natural phytohormone reportedly exerts anti-inflammatory and anti-oxidative properties in diabetes and colitis. However, the efficacy of ABA against allergic airway inflammation and the underlying mechanism remain unknown. Herein, an OVA-induced murine allergic airway inflammation model was established and treated with ABA in the presence or absence of PPAR-γ antagonist GW9662. The results showed that ABA effectively stunted the development of airway inflammation, and concordantly downregulated OVA-induced activation of NLRP3 inflammasome, suppressed oxidative stress and decreased the expression of mitochondrial fusion/fission markers including Optic Atrophy 1 (OPA1), Mitofusion 2 (Mfn2), dynamin-related protein 1 (DRP1) and Fission 1 (Fis1). Moreover, ABA treatment further increased OVA-induced expression of PPAR-γ, while GW9662 abrogated the inhibitory effect of ABA on allergic airway inflammation as well as on the activation of NLRP3 inflammasome and oxidative stress. Consistently, ABA inhibited the activation of NLRP3 inflammasome, suppressed oxidative stress and mitochondrial fusion/fission in LPS-stimulated Raw264.7 cells via PPAR-γ. Collectively, ABA ameliorates OVA-induced allergic airway inflammation in a PPAR-γ dependent manner, and such effect of ABA may be associated with its inhibitory effect on NLRP3 inflammasome and oxidative stress. Our results suggest the potential of ABA or ABA-rich food in protecting against asthma.
脱落酸（ABA）是一种众所周知的天然植物激素，据报道其在糖尿病和结肠炎中具有抗炎和抗氧化作用。然而，ABA 对过敏性气道炎症的疗效及其潜在机制尚不清楚。在此，我们建立了 OVA 诱导的小鼠过敏性气道炎症模型，并在存在或不存在 PPAR-γ 拮抗剂 GW9662 的情况下用 ABA 进行治疗。结果表明，ABA 可有效抑制气道炎症的发展，并下调 OVA 诱导的 NLRP3 炎性体的激活，抑制氧化应激并降低线粒体融合/分裂标志物的表达，包括光感受器萎缩症 1（OPA1）、线粒体融合蛋白 2（Mfn2）、动力相关蛋白 1（DRP1）和分裂蛋白 1（Fis1）。此外，ABA 处理进一步增加了 OVA 诱导的 PPAR-γ 的表达，而 GW9662 消除了 ABA 对过敏性气道炎症以及 NLRP3 炎性体激活和氧化应激的抑制作用。一致地，ABA 通过 PPAR-γ 抑制 LPS 刺激的 Raw264.7 细胞中 NLRP3 炎性体的激活、抑制氧化应激和线粒体融合/分裂。总之，ABA 通过 PPAR-γ 依赖的方式改善 OVA 诱导的过敏性气道炎症，ABA 的这种作用可能与其对 NLRP3 炎性体和氧化应激的抑制作用有关。我们的研究结果表明 ABA 或富含 ABA 的食物具有预防哮喘的潜力。
