Target analysis and identification of curcumin against vascular calcification

• Published in: Scientific reports 2024-07, Vol.14 (1), p.17344-12, Article 17344
• Main Authors: Li, Qingjie, Zhou, Qiaofeng, Li, Shihuan, Li, Suqin, Liao, Wenli, Yu, Liangzhu, Liu, Chao, Li, Mincai, Xia, Hongli
• Format: Article
• Language: English
• Subjects: 631/154; 692/308; 692/4019; 692/420; 692/499; 692/699; AKT protein; Animal research; Animals; Arteriosclerosis; Bcl-2 protein; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; BCL2; Bone Morphogenetic Protein 2 - genetics; Bone Morphogenetic Protein 2 - metabolism; Calcification; Calcification (ectopic); Calcium; Cbfa-1 protein; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Curcumin; Curcumin - pharmacology; Disease Models, Animal; EGFR; Epidermal growth factor receptors; ErbB Receptors - metabolism; Gene set enrichment analysis; Humanities and Social Sciences; Male; Molecular Docking Simulation; multidisciplinary; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Protein Interaction Maps - drug effects; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; RUNX2; Science; Science (multidisciplinary); Signal Transduction - drug effects; STAT3; Stat3 protein; STAT3 Transcription Factor - metabolism; Vascular calcification; Vascular Calcification - drug therapy; Vascular Calcification - metabolism; Vascular Calcification - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-67776-2

To investigate the mechanism of curcumin (CUR) on vascular calcification (VC), we screen for common targets of CUR and atherosclerosis and verify the targets genes in vivo and in vitro experiments. The common targets of CUR and AS were screened and obtained using different databases. These target genes were analyzed by GO and KEGG pathway enrichment analysis. PPI network analysis was performed and to analyze the key targets. A rat VC model was constructed and CUR was fed for three weeks. The changes of vascular structure and calcium salt deposition were observed in H&E and Von Kossa staining. Further, the expression of these target proteins was detected in the primary VSMCs of VC. The 31 common targets were obtained. GO functional enrichment analysis obtained 1284 terms and KEGG pathway enriched 66 pathways. The key genes were identified in the cytoHubba plugin. The molecular docking analysis showed that CUR bound strongly to EGFR, STAT3 and BCL2. The animal experiments showed the deposition calcium salt reduced by the CUR administration. These proteins BMP2, RUNX2, EGFR, STAT3 and BAX expression were upregulated in VC group and CUR attenuated the upregulated expression. The signal protein Akt and p65 expression increased in VC group and decreased in CUR group. We identified some common target genes of CUR and AS and identified these key genes. The anti-VC effect of CUR was associated with the inhibition of upregulation of EGFR, STAT3 and RUNX2 expression in VSMCs.