Wang Kongyan, Hu Huiyu, Xu Zaibin, Chen Yan, Qiu Yi, Hu Yingjie, Huang Jiawen, Luo Zhuohui
Hainan Pharmaceutical Research and Development Science Park, Hainan Medical University, Haikou 571199, China.
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Biology (Basel). 2025 Sep 2;14(9):1170. doi: 10.3390/biology14091170.
Acute lung injury (ALI) is a serious respiratory condition. The natural compound 7-Methoxyflavanone (7MF) has a broad spectrum of anti-inflammatory and antioxidant properties. However, its pharmacological effects and underlying mechanisms in alleviating ALI remain poorly understood.
An in vitro LPS-induced RAW264.7 macrophage inflammatory injury assay and an in vivo lipopolysaccharide (LPS)-induced ALI assay in mice were conducted.
In vitro experiments showed that 7MF significantly reduced levels of IL1β, IL6, and TNF-α; decreased the expression of COX2 and iNOS, as well as TLR4 and MyD88; suppressed the phosphorylation and degradation of IκBα; and blocked the entry of NF-κB p65 into the nucleus, thereby inhibiting NF-κB signaling. Meanwhile, 7MF also decreased ROS levels; prevented the dissociation of Txnip from Trx-1; and suppressed NLRP3, Caspase-1, Cleaved Caspase-1 p10, NEK7, Caspase-8, Cleaved Caspase-8, IL18, GSDMD, and GSDMD N-terminal expression, and thus inhibited NLRP3 signaling. MCC950, a specific inhibitor of NLRP3, significantly enhanced the pharmacological inhibition of NLRP3 by 7MF. Notably, similar results were confirmed in LPS-induced ALI experiments in mice.
The compound 7MF effectively alleviated LPS-induced ALI by suppressing TLR4/NF-κB p65 and ROS/Txnip/NLRP3 signaling pathways. Our findings provide scientific evidence for drug development and treatment of ALI.
急性肺损伤（ALI）是一种严重的呼吸系统疾病。天然化合物7-甲氧基黄酮（7MF）具有广泛的抗炎和抗氧化特性。然而，其在减轻ALI方面的药理作用和潜在机制仍知之甚少。
进行了体外脂多糖（LPS）诱导的RAW264.7巨噬细胞炎症损伤试验以及体内LPS诱导的小鼠ALI试验。
体外实验表明，7MF显著降低了IL1β、IL6和TNF-α的水平；降低了COX2和iNOS以及TLR4和MyD88的表达；抑制了IκBα的磷酸化和降解；并阻止了NF-κB p65进入细胞核，从而抑制了NF-κB信号通路。同时，7MF还降低了活性氧水平；阻止了Txnip与Trx-1的解离；并抑制了NLRP3、Caspase-1、裂解的Caspase-1 p10、NEK7、Caspase-8、裂解的Caspase-8、IL18、GSDMD和GSDMD N端的表达，从而抑制了NLRP3信号通路。NLRP3的特异性抑制剂MCC950显著增强了7MF对NLRP3的药理抑制作用。值得注意的是，在LPS诱导的小鼠ALI实验中也证实了类似的结果。
化合物7MF通过抑制TLR4/NF-κB p65和ROS/Txnip/NLRP3信号通路有效减轻了LPS诱导的ALI。我们的研究结果为ALI的药物开发和治疗提供了科学依据。
