Multi-Target Anti-Inflammatory Potential of Amentoflavone and Hypericin: Molecular Docking with TNF-α, iNOS, JAK3, and Prostaglandin Enzymes

Multiple signaling pathways, including cytokine regulation, nitric oxide production, and prostaglandin biosynthesis, drive chronic inflammation. Natural polyphenolic compounds are promising therapeutic candidates due to their multitarget potential and favorable safety profiles. Here, we performed molecular docking of amentoflavone and hypericin against key inflammatory targets: TNF-α (PDB: 2AZ5), inducible nitric oxide synthase – iNOS (PDB: 3E7G), tyrosine-protein kinase JAK3 (PDB: 6HZV), prostaglandin E synthase (PDB: 4AL1), and prostaglandin reductase 3 (PDB: 7ZEJ). Both compounds exhibited strong binding affinities, in several cases surpassing native ligands. Amentoflavone showed the highest affinity for iNOS and prostaglandin reductase, while hypericin strongly targeted JAK3 and TNF-α. Overall, both natural products demonstrate the ability to bind with higher affinity and potentially greater stability than the native ligands, making them promising candidates for further experimental validation. Our findings suggest that Amentoflavone and Hypericin are potential multi-target anti-inflammatory agents that could serve as natural therapeutic options for chronic inflammatory diseases, although further in vitro and in vivo studies are required.