Exploring Anti-inflammatory Targets of Flavonoids through Integrated Molecular Docking and Network Pharmacology

Inflammation is a complex physiological response associated with numerous diseases. Flavonoids, a class of natural compounds widely distributed in plants, have demonstrated promising anti-inflammatory properties. However, their comprehensive mechanisms of action and potential molecular targets remain indefinable. In the present study, we employed a network pharmacology approach combined with molecular docking to investigate the anti-inflammatory effects of some flavonoids. Initially, we collected and curated a comprehensive database such as ADMET parameters and targets from Swiss ADME, ADMET 2.O and Swiss target predication. We further constructed a protein-protein interaction network to identify key proteins involved in inflammation by using string database. Subsequently, we integrated the flavonoid dataset with the protein network to establish potential flavonoid-protein interactions by using Cytosacpe vina. The GO and KEGG enrichment analysis were done with the help of David database. Molecular docking was accomplished through Autodock Vina, and assessed the binding affinity of selected flavonoids towards the identified target proteins. The docking analysis provided insights into the specific interactions between flavonoids and target proteins, elucidating the potential mechanisms underlying their anti-inflammatory effects. The bioactive components ferulic acid, quercetin, rutin and hesperidin modulates many molecular and cellular processes and then exerts anti-inflammatory effects. From the analysis the key targets were participated in inflammatory bowel disease, IL 17 signaling pathway, TNF signaling pathway, cytokine-mediated signaling pathway, rheumatoid arthritis, lipopolysaccharides etc. Further molecular docking studies also revealed that binding affinity of selected flavonoids were higher than that of diclofenac.