Therapeutic Potential of Clove and Cinnamon Essential Oils in Diabetic Foot Ulcer: A Network Pharmacology and Molecular Dynamics Study

Abstract Diabetic foot ulcers (DFU), a severe complication of diabetes mellitus (DM), pose significant global health challenges due to their impaired healing, heightened risk of infections, and potential for limb amputation. Pathophysiological factors contributing to DFUs include compromised immune responses, vascular insufficiency, and extracellular matrix degradation, with a notable upregulation of matrix metalloproteinase‐9 (MMP9) and suppressed PI3K/Akt‐mediated angiogenic signaling. This study explores the pharmacological potential of bioactive constituents in clove and cinnamon essential oils for DFU management through network pharmacology and molecular dynamics approaches. From an initial pool of 126 compounds, 15 were selected based on favorable drug‐likeness with good bioavailability criteria. Gene target analysis and protein‐protein interaction (PPI) network assessments identified AKT1 and MMP9 as pivotal modulators in DFU pathology. Molecular docking demonstrated high‐affinity interactions, with Stigmasterol and Campesterol binding to AKT1 , potentially augmenting angiogenesis and cellular resilience, while Oleanolic acid and Luteolin exhibited strong binding affinities to MMP9, implying a role in mitigating extracellular matrix degradation. Molecular dynamics simulations validated the structural stability of these ligand‐protein complexes. Binding free energy calculations via MM/PBSA analysis reinforced the therapeutic promise of these interactions. Further in vitro validation using relevant cell models including antimicrobial tests, is imperative.