Based on network pharmacology methods, we explored the mechanism of the classic Chinese medicine formula Coix seed decoction (CSD) in treating knee osteoarthritis (KOA). We searched each single drug in the CSD in the traditional Chinese medicine systematic pharmacology database in turn to obtain information on the active ingredients and target proteins of the CSD, and obtain the name of the genes corresponding to the target proteins through the UniProt database. We collected KOA-related genes from DisGeNET, GeneCards, comparative toxicogenomics database, and MalaCards database. The Venny online tool identified potential therapeutic targets by intersecting CSD and KOA target genes, while gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed using the Oebiotech Cloud Platform. A protein-protein interaction network was established using the String database; a “CSD-active ingredient-target gene-KOA” network plot was constructed using Cytoscape 3.9.1 software and screened for key targets and hub targets. Finally, molecular docking was performed for hub genes with high Degree values. A total of 227 effective target genes for CSD and 8816 KOA-related target genes were obtained, as well as 191 cross-target genes for CSD and KOA. We screened 37 key gene targets and identified the top 10 hub target genes in descending order of Degree value using protein-protein interaction and Cytoscape 3.9.1 software (TNF, IL-6, MMP-9, IL-1β, AKT-1, VEGFα, STAT-3, PTGS-2, IL-4, TP53). Gene ontology analysis showed that the biological process of CSD treatment of KOA mainly involves cytokine-mediated signaling pathway, negative regulation of apoptotic process, cellular response to hypoxia, cellular response to cadmium ion, response to estradiol, and extrinsic apoptotic signaling pathway in absence of ligand. Kyoto encyclopedia of genes and genomes analysis revealed major signaling pathways including Cellular senescence, TNF signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results show that the core components bind well to the core targets. In conclusion, CSD may exert therapeutic effects on KOA by inhibiting pathological processes such as inflammatory response, apoptosis, cellular senescence, and oxidative stress.
Osteoarthritis (OA) causes pain and disability in the elderly and has placed a severe burden on healthcare worldwide. Excessive death and decreased density of chondrocytes are recognized as the major pathological characteristic of OA. Chondrocytes have been shown to have multiple forms of death, including apoptosis, pyroptosis, necroptosis, and ferroptosis. The excessive death of chondrocytes often forms a vicious circle with imbalanced chondrocytes extracellular matrix (ECM) metabolism. Therefore, inhibiting chondrocytes excessive death has become a key point that cannot be ignored in the development of OA treatment strategies. We summarized recent studies on the functions and mechanisms of different modes of chondrocyte death and potential therapeutic strategies for OA and offered our views. This may provide direction and theoretical support for formulating OA treatment strategies in the future.
Objective, With the help of network pharmacology and in vitro studies, this study aims to understand the mechanism by which Epimedium/ Icariin (EPI/ICA) promote angiogenesis through the HIF-1 signaling pathway, laying the groundwork for the treatment of bone discontinuity. Methods, 1) The TCMSP database provided the gene targets for Epimedium's effect in this investigation. Search the GeneCards database for gene targets associated with "bone discontinuity". GO, KEGG, and Reactome enrichment analysis is performed after identifying possible gene targets for EPI/ICA treatment of bone discontinuity. Molecular docking to confirm the HIF-1 pathway's essential proteins' capacity to bind to ICA. 2) ①. Human umbilical vein vascular endothelial cells (HUVECs) were divided into blank control groups and ICA groups with different concentrations (0.01, 0.1, 1, 10 mol/L), and CCK8 measured the proliferative activity of HUVECs in each group after ICA intervention. These in vitro experiments sought to identify the optimal intervention concentration of ICA. ②. A test for angiogenesis to determine whether it can encourage angiogenesis. ③. After ICA intervention, Western blot and Elisa measured the level of HIF-1 pathway-related protein activity in each group. Results, For the treatment of bone discontinuity, the bioinformatic analysis of EPI/ICA identified 164 potential therapeutic gene targets, including 45 important gene targets and 10 of these crucial gene targets (HIF1A, AKT1, TPT3, IL6, TNF, VEGFA, CASP3, MYC, EGFR, ESR1). The biological mechanisms examined in the GO of EPI/ICA for the treatment of osteonecrosis act primarily through the regulation of angiogenesis and the negative regulation of apoptotic processes, according to enrichment analysis of 45 important gene targets. The HIF-1 signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and other signaling pathways were found to be primarily involved in the regulation of the EPI/ICA process in the therapy of bone discontinuity, according to KEGG analysis. Reactome enrichment analysis showed that the regulation of the EPI/ICA treatment of bone discontinuity mostly involves the regulation of inflammatory factors that are similar to interleukin and the body's autoimmune system. According to the results of molecular docking, ICA binds efficiently to the important target proteins of the HIF-1 signaling pathway, HIF-1A, VEGF, and IL-6. Further research revealed that ICA, the active ingredient in Epimedium, might increase the value-added differentiation of HUVECs, with the potential mechanism being angiogenesis via the HIF-1 signaling pathway. Conclusion: This research revealed that EPI/ICA controls HIF-1A, VEGF, and IL-6, which are important HIF-1 signaling pathway target proteins, increases the value-added differentiation of HUVECs and angiogenesis, and offers a new approach for the treatment of bone discontinuity using EPI/ICA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.