In Silico Characterization of Bee Pollen Phytochemicals SupportingCobalt Nanoparticle Mediated Chronic Wound Healing

Abstract

The present study explores the molecular mechanisms underlying
the wound-healing efficacyof bee-pollen-derived phytochemicals
that contribute to the biosynthesis and biological function
of cobalt nanoparticles (CoNPs). Building upon our experimental findings, in which bee pollen aqueous extract (BPAE) served as both a reducing and stabilizing agent for CoNP formation, this in silico investigation identified key bioactive constituents and their potential interactions with chronic wound-associated biomarkers. Gas chromatography-mass spectrometry
(GC-MS) analysis revealed compounds such as diethyl carbitol, (S)-(+)-2-amino-3-methyl-1-butanol, and propanal (2,3- dihydroxy-, S-), which were further evaluated through molecular docking against selected wound-healing targets including tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9). Among these ligands, diethyl carbitol exhibited the highest binding affinity (−4.5 kcal mol−1), forming hydrogen-bond interactions with residues ASP833 and VAL753, indicating strong anti-inflammatory and tissue regenerative potential. Absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetic profiling further confirmed drug-likeness, moderate
aqueous solubility, and favorable oral bioavailability, with a bioavailability score of 0.55. Collectively, these findings highlight how deterministic biomolecular interactions and stochastic conformational variations jointly influence ligand–receptor stability, supporting the dual-mechanism
hypothesis proposed for CoNP-mediated therapeutic action. This integrative in vitro–in silico framework provides mechanistic insight into the synergistic role of bee-pollen phytochemicals in nanoparticleassisted wound healing and offers a rational platform for the development of natureinspired nanotherapeutics.