Mechanism by which luteolin inhibits silicotic fibrosis through binding to the BCL-2 protein
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.
国家科技期刊平台
NSTL
万方数据
