Jing Yifan, Bai Ying, Liang Chao, Liu Yafeng, Zhou Jiawei, Guo Jianqiang, Cai Xiaolong, Hu Xiaofei, Fang Yujing, Ding Xuansheng, Wu Jing, Hu Dong
Department of Immunology, School of Medicine, Anhui University of Science and Technology, Huainan City, China; Anhui Province Engineering Laboratory of Occupational Health and Safety, School of Medicine, Anhui University of Science and Technology, Huainan City, China.
Department of Immunology, School of Medicine, Anhui University of Science and Technology, Huainan City, China; Anhui Province Engineering Laboratory of Occupational Health and Safety, School of Medicine, Anhui University of Science and Technology, Huainan City, China; Huainan Xinhua Medical Group Xinhua Hospital, China.
Cell Signal. 2025 Jul;131:111780. doi: 10.1016/j.cellsig.2025.111780. Epub 2025 Mar 28.
Silicosis, formerly known as silico, is an irreversible disease caused by prolonged inhalation of substantial amounts of free crystalline silica dust, characterized by pulmonary inflammation and extensive nodular fibrosis. The etiology of the disease remains unclear, which currently hinders the development of effective therapeutic drugs and interventions. Ingenol (Ing), a terpenoid active ingredient found in plants of the Euphorbiaceae family, including the entire herb of Euphorbia helioscopia, Euphorbia kansui, or Euphorbia lathyris, demonstrates significant anti-inflammatory and antiviral activities. In this study, we identified and confirmed that Ingenol can significantly ameliorate silicosis induced by silica dioxide by inhibiting the PTGS2/PI3K/AKT signaling pathway. In vivo, Ingenol improves pulmonary respiratory function and reduces inflammation and fibrosis in a murine model of CS-induced silicosis. In vitro, Ingenol inhibits the expression of cellular factors associated with inflammation and fibrosis, as well as macrophage apoptosis and fibroblast migration. Furthermore, it can modulate the expression of fibrosis-related proteins, thereby inhibiting CS-induced fibrotic responses. Mechanistically, a combination of bioinformatics, network pharmacology, and experimental validation indicates that Ingenol mitigates the progression of silicosis by modulating the PTGS2/PI3K/AKT signaling pathway. In summary, these findings suggest that Ingenol is a potential candidate for the treatment of silicosis.
矽肺，以前称为硅肺，是一种因长期吸入大量游离结晶二氧化硅粉尘而导致的不可逆疾病，其特征为肺部炎症和广泛的结节性纤维化。该疾病的病因仍不清楚，这目前阻碍了有效治疗药物和干预措施的开发。千金二萜醇（Ing）是一种在大戟科植物中发现的萜类活性成分，包括泽漆全草、甘遂或续随子，具有显著的抗炎和抗病毒活性。在本研究中，我们鉴定并证实千金二萜醇可通过抑制PTGS2/PI3K/AKT信号通路显著改善二氧化硅诱导的矽肺。在体内，千金二萜醇可改善矽肺小鼠模型的肺呼吸功能，并减轻炎症和纤维化。在体外，千金二萜醇可抑制与炎症和纤维化相关的细胞因子表达，以及巨噬细胞凋亡和成纤维细胞迁移。此外，它还可调节纤维化相关蛋白的表达，从而抑制二氧化硅诱导的纤维化反应。从机制上讲，生物信息学、网络药理学和实验验证相结合表明，千金二萜醇通过调节PTGS2/PI3K/AKT信号通路减轻矽肺的进展。总之，这些发现表明千金二萜醇是治疗矽肺的潜在候选药物。
