Background Chronic inflammation is at the centre of the pathogenesis of numerous diseases through the promotion of dysregulated immune responses by intricate cytokine networks, with Tumour Necrosis Factor (TNF) being a central mediator. Though TNF-targeted treatments are effective, they induce side effects and expense, which generates enthusiasm for natural compounds as safer substitutes. Baicalein, a flavonoid derived from Scutellaria baicalensis, is anti-inflammatory in nature but with an uncertain mode of action on the TNF signaling pathway. In this study, network pharmacology and molecular docking were utilized to determine the interaction of Baicalein with TNF receptors and ligands, with the aim of revealing its multitarget modulatory effect on prominent inflammatory pathways.
Methods A network pharmacology-driven strategy was employed, integrating target prediction, protein–protein interaction analysis, KEGG pathway enrichment, and molecular docking simulations to explore Baicalein's action on TNF signaling.
Results Docking results revealed Baicalein’s strong affinity with TNFR1 (-9.1 kcal/mol), TNFR2 (-8.7 kcal/mol), TNF-α (-8.4 kcal/mol), and TNF-β (-7.9 kcal/mol). Pathway analysis showed modulation of TNF-associated networks, including NF-κB, MAPK, and PI3K-Akt pathways. Network maps and mechanistic diagrams demonstrated Baicalein’s multitarget effects.
Conclusion Baicalein demonstrates significant multitarget activity through modulation of the TNF axis, highlighting its therapeutic potential in chronic inflammatory diseases.
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