RESUMEN
BACKGROUND: Legg-Calvé-Perthes disease is a special self-limited disease in pediatric orthopedics with a high disability rate and a long-term course, and there is still no clear and effective therapeutic drug in clinic. This study aimed to investigate the potential efficacy of biochanin A, a kind of oxygen-methylated isoflavone compound, in treating Perthes disease based on network pharmacology, molecular docking and in vitro experiments. METHODS: IL-6 was used to stimulate human umbilical vein endothelial cells to construct endothelial cell dysfunction model. We demonstrated whether biochanin A could alleviate endothelial dysfunction through CCK8 assay, immunofluorescence. Targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. Targets of endothelial dysfunction were obtained from Genecards and OMIM databases. Protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomics analyses were used to analyze the potential target and the key pathway of the anti-endothelial dysfunction activity of biochanin A. To validate the potential target-drug interactions, molecular docking and molecular dynamics simulations were performed and the result was proved by western blot. RESULTS: It was found that biochanin A can promote the expression of ZO-1, reduce the expression of ICAM-1, which means improving endothelial dysfunction. A total of 585 targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. A total of 10,832 targets of endothelial dysfunction were obtained from Genecards and OMIM databases. A total of 527 overlapping targets of endothelial dysfunction and biochanin A were obtained. AKT1, TNF-α, VCAM1, ICAM1, and NOS3 might be the key targets of the anti-endothelial dysfunction activity of biochanin A, and the key pathways might be PI3K-Akt and TNF signaling pathways. Molecular docking results indicated that the AKT1 and TNF-α had the highest affinity binding with biochanin A. CONCLUSION: This study indicates that biochanin A can target AKT1 and TNF-α to alleviate endothelial dysfunction induced by IL-6 in Perthes disease, which provides a theoretical basis for the treatment of Perthes disease by using biochanin A.
Asunto(s)
Enfermedad de Legg-Calve-Perthes , Factor de Necrosis Tumoral alfa , Niño , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Células Endoteliales , Interleucina-6 , Fosfatidilinositol 3-QuinasasRESUMEN
Objective: To summarize the regulatory effect of non-coding RNA (ncRNA) on type H vessels angiogenesis of bone. Methods: Recent domestic and foreign related literature about the regulation of ncRNA in type H vessels angiogenesis was widely reviewed and summarized. Results: Type H vessels is a special subtype of bone vessels with the ability to couple bone formation. At present, the research on ncRNA regulating type H vessels angiogenesis in bone diseases mainly focuses on microRNA, long ncRNA, and small interfering RNA, which can affect the expressions of hypoxia inducible factor 1α, platelet derived growth factor BB, slit guidance ligand 3, and other factors through their own unique ways of action, thus regulating type H vessels angiogenesis and participating in the occurrence and development of bone diseases. Conclusion: At present, the mechanism of ncRNA regulating bone type H vessels angiogenesis has been preliminarily explored. With the deepening of research, ncRNA is expected to be a new target for the diagnosis and treatment of vascular related bone diseases.