Zhang Beibei, Zeng Mengnan, Tie Qimei, Wang Ru, Wang Mengya, Wu Yuanyuan, Zheng Xiaoke, Feng Weisheng
Henan University of Chinese Medicine, 156 Jinshui East Road, Zhengzhou 450046, China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, 156 Jinshui East Road, Zhengzhou 450046, China; Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan province and Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Henan University of Chinese Medicine, 156 Jinshui East Road, Zhengzhou 450046, China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, 156 Jinshui East Road, Zhengzhou 450046, China.
Int Immunopharmacol. 2025 Jan 10;144:113708. doi: 10.1016/j.intimp.2024.113708. Epub 2024 Dec 3.
(-)-Epigallocatechin-3-gallate (EGCG) is a polyphenol in green tea with potential lung-protective effects. However, the effects of EGCG on airway inflammation in asthma remain unclear. The aim of this study was to investigate the effect and mechanism of EGCG on asthmatic airway inflammation. In this study, the therapeutic effects of EGCG on ovalbumin (OVA)-induced asthmatic mice were tested first. Second, the effects of EGCG on airway inflammation, airway hyperresponsiveness (AHR), airway mucus hypersecretion, cell apoptosis and differential genes were investigated. Finally, the relationships between the effects of EGCG on airway inflammation and the TNF-α/TNF-R1/NLRP3 signaling pathway in asthmatic mice were explored. The results showed that EGCG could attenuate AHR, alleviate the symptoms of alveolar wall thickening and inflammatory cell infiltration, decrease the levels of inflammatory cytokines and airway mucus markers, reduce apoptosis and reactive oxygen species (ROS) and increase the mitochondrial membrane potential (MMP) in primary lung cells in asthmatic mice. Additionally, EGCG significantly inhibited the activation of the TNF-α/TNF-R1/NLRP3 signaling pathway in the lung tissues of asthmatic mice. The lowest binding free energies of EGCG with TNF-α, TNF-R1 and NLRP3 were -11.6, -11.6 and -8.2 kcal/mol, respectively. Moreover, the equilibrium dissociation constant (KD) of EGCG and TNF-R1was 26.05 μmol/L. EGCG-mediated inhibition of TNF-α/TNF-R1/NLRP3 signaling pathway activation was blocked in LPS-induced BEAS-2B and RAW264.7 cells overexpressing TNF-α. Consequently, EGCG effectively attenuated AHR and inhibited airway inflammation and airway mucus hypersecretion in asthmatic mice, and these effects may be closely related to the TNF-α/TNF-R1/NLRP3 signaling pathway.
（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶中的一种多酚，具有潜在的肺保护作用。然而，EGCG对哮喘气道炎症的影响仍不清楚。本研究旨在探讨EGCG对哮喘气道炎症的作用及机制。在本研究中，首先测试了EGCG对卵清蛋白（OVA）诱导的哮喘小鼠的治疗效果。其次，研究了EGCG对气道炎症、气道高反应性（AHR）、气道黏液高分泌、细胞凋亡和差异基因的影响。最后，探讨了EGCG对哮喘小鼠气道炎症的影响与TNF-α/TNF-R1/NLRP3信号通路之间的关系。结果表明，EGCG可减轻AHR，缓解肺泡壁增厚和炎性细胞浸润症状，降低炎性细胞因子和气道黏液标志物水平，减少凋亡和活性氧（ROS），并增加哮喘小鼠原代肺细胞的线粒体膜电位（MMP）。此外，EGCG显著抑制哮喘小鼠肺组织中TNF-α/TNF-R1/NLRP3信号通路的激活。EGCG与TNF-α、TNF-R1和NLRP3的最低结合自由能分别为-11.6、-11.6和-8.2千卡/摩尔。此外，EGCG与TNF-R1的平衡解离常数（KD）为26.05微摩尔/升。在LPS诱导的过表达TNF-α的BEAS-2B和RAW264.7细胞中，EGCG介导的TNF-α/TNF-R1/NLRP3信号通路激活的抑制作用被阻断。因此，EGCG有效减轻了哮喘小鼠的AHR，抑制了气道炎症和气道黏液高分泌，这些作用可能与TNF-α/TNF-R1/NLRP3信号通路密切相关。
