兰州大学学报（医学版）2024，Vol.50Issue(8)：7-15,9.DOI:10.13885/j.issn.1000-2812.2024.08.002
木犀草素通过与B淋巴细胞瘤-2蛋白结合抑制硅肺纤维化的作用机制
Mechanism by which luteolin inhibits silicotic fibrosis through binding to the BCL-2 protein
摘要
Abstract
Objective To explore the potential and mechanism of the active components of the traditional Chinese medicine Salvia miltiorrhiza(Danshen)in the treatment of silicosis.Methods Network pharmacology and molecular docking approaches were employed to identify the bioactive constituents and critical molecular targets of Danshen for its therapeutic potential in teating silicosis.The cellular thermal shift assay was used to test the binding stability of the effective components with key targets,cell scratch assays were used to test the migration ability of epithelial cells,and Western Blotting analysis was conducted to quantify the expression profiles of markers indicative of epithelial-mesenchymal transition,fibrosis and proteins associated with apoptosis.Results Network pharmacology and molecular docking identified luteolin,an effective component of Danshen,as having the lowest binding energy with the key silicosis target B cell lymphoma-2(BCL-2).Subsequently,cellular thermal shift assay experiments confirmed that luteolin had a good binding stability with BCL-2 protein.Phenotypically,cell scratch assays showed that luteolin could inhibit the migration of epithelial cells stimulated by transforming growth factor-β1.Western Blotting experiments demonstrated that luteolin could inhibit the expression of BCL-2 protein,and,compared to the transforming growth factor-β1 stimulation group,luteolin administration and BCL-2 silencing could inhibit epithelial-mesenchymal transi-tion and collagen formation,thereby inhibiting the progression of fibrosis.Mechanistically,luteolin adminis-tration and BCL-2 silencing could promote apoptosis.Conclusion Luteolin can bind to BCL-2 and inhibit the progression of silicosis fibrosis,and its mechanism of action may be related to its ability to promote apoptosis.关键词
网络药理学/硅肺/木犀草素/B淋巴细胞瘤-2/上皮间质转化/细胞凋亡Key words
network pharmacology/silicosis/luteolin/B cell lymphoma-2/epithelial-mesenchymal transition/apoptosis分类
基础医学引用本文复制引用
李芸芸,丁选胜,周家伟,刘紫琴,杨雪莲,刘亚锋,郭健强,胡东,吴静..木犀草素通过与B淋巴细胞瘤-2蛋白结合抑制硅肺纤维化的作用机制[J].兰州大学学报（医学版）,2024,50(8):7-15,9.基金项目
国家自然科学基金资助项目(81971483) （81971483）
安徽高校协同创新基金资助项目(GXXT-2020-058) （GXXT-2020-058）
工业粉尘深度净化与职业健康安全安徽普通高校重点实验室开放基金资助项目(AYZJSGXLK202202002) （AYZJSGXLK202202002）
安徽理工大学引进人才基金资助项目(2022yjrc14) （2022yjrc14）
安徽理工大学研究生创新基金资助项目(2023cx2149) （2023cx2149）
