Wang Lu, Tang Ying, Hou Tianhua, Gao Yun, Ci Xinxin, Peng Liping
Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021 China.
Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130001 China.
Int Immunopharmacol. 2025 Feb 20;148:114123. doi: 10.1016/j.intimp.2025.114123. Epub 2025 Jan 29.
Fine particulate matter (PM2.5) is a global environmental problem that threatens public health because it can induce ferroptosis and cause lung injury. Hesperetin (Hes), a natural compound widely present in fruits and vegetables, can activate nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting powerful antioxidant effects.
We explored the antioxidant effects of Hes on lung injury caused by PM2.5 exposure.
In vivo, a mouse model of PM2.5-induced lung injury was used to evaluate the protective effect of Hes. In vitro, the effects of Hes on PM2.5-induced ferroptosis were examined in BEAS-2B cells.
In vivo, Hes activated the Nrf2 signaling pathway and protected lung tissues from damage induced by PM2.5. In vitro, Hes activated Nrf2 by promoting PI3K/AKT phosphorylation and inhibiting PM2.5-induced ferroptosis. However, in siNrf2-treated BEAS-2B cells, the protective effects of Hes were eliminated. In addition, Nrf2-KO mice exhibited more severe lung injury than did wild-type (WT) mice after PM2.5 exposure. Besides, the protective effects of Hes on PM2.5-exposed Nrf2-KO mice were strongly compromised.
Hes activates Nrf2 by promoting PI3K/AKT phosphorylation to exert a protective effect on PM2.5-induced ferroptosis and lung injury.
细颗粒物（PM2.5）是一个全球性环境问题，因其可诱导铁死亡并导致肺损伤，从而威胁公众健康。橙皮素（Hes）是一种广泛存在于水果和蔬菜中的天然化合物，可激活核因子红细胞2相关因子2（Nrf2），从而发挥强大的抗氧化作用。
我们探讨了橙皮素对PM2.5暴露所致肺损伤的抗氧化作用。
在体内，使用PM2.5诱导的小鼠肺损伤模型评估橙皮素的保护作用。在体外，在BEAS-2B细胞中检测橙皮素对PM2.5诱导的铁死亡的影响。
在体内，橙皮素激活Nrf2信号通路，保护肺组织免受PM2.5诱导的损伤。在体外，橙皮素通过促进PI3K/AKT磷酸化激活Nrf2，并抑制PM2.5诱导的铁死亡。然而，在经siNrf2处理的BEAS-2B细胞中，橙皮素的保护作用消失。此外，PM2.5暴露后，Nrf2基因敲除（KO）小鼠比野生型（WT）小鼠表现出更严重的肺损伤。此外，橙皮素对PM2.5暴露的Nrf2-KO小鼠的保护作用也大大受损。
橙皮素通过促进PI3K/AKT磷酸化激活Nrf2，对PM2.5诱导的铁死亡和肺损伤发挥保护作用。
