Apigenin Alleviates Ligamentum Flavum Ossification by Dual-Targeting CA9 and CDK6 and Modulating Calcium/PI3K-Akt Signaling.
TL;DR
An integrated computational strategy combining network pharmacology, machine learning, and molecular docking was used to study apigenin's therapeutic potential for OLF, offering initial insights into how apigenin may modulate OLF.
Abstract
While apigenin shows therapeutic potential for bone-related disorders like osteoporosis and osteoarthritis, its mechanisms in regulating ligamentum flavum ossification (OLF) are unclear. An integrated computational strategy combining network pharmacology, machine learning, and molecular docking was used to study apigenin's therapeutic potential for OLF. First, differential gene expression profiling was done using the GSE113212 dataset to find OLF-related differentially expressed genes. At the same time, apigenin's putative targets and bioactive components were collected from pharmacological databases and literature. Common targets between apigenin and OLF-related genes were identified by Venn diagram analysis. Then, the Metascape platform was used to analyze the functional enrichment of these overlapping targets, including Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses. The results showed significant involvement in bone-metabolism and inflammatory-response biological processes and signaling pathways, especially the calcium and PI3K-Akt signaling pathways. A protein-protein interaction network was built with the STRING database and refined by machine-learning algorithms to find central therapeutic targets. Molecular docking analysis showed binding energies of <-5 kcal/mol between apigenin and core target proteins, indicating strong binding. Molecular dynamics simulations supported the stability and binding reliability of apigenin-target complexes. Overall, these results offer initial insights into how apigenin may modulate OLF, highlighting new therapeutic strategies and potential targets for OLF treatment.