Molecular docking-guided identification of multi-target anti-inflammatory phytochemicals from almond (Prunus dulcis) gum and experimental validation of almond gum-mediated silver/zinc oxide nanobiocomposites for accelerated wound healing.

Wound healing is a complex biological process where uncontrolled inflammation often delays tissue repair, imposing a significant clinical and economic burden worldwide. This study aimed to develop and evaluate almond gum (Prunus dulcis) based silver and zinc oxide nanobiocomposites (AG-Ag and AG-ZnO) through integrated computational, In-vitro and In-vivo studies as a promising therapeutic approach for accelerating wound healing. This study is the first to comparatively evaluate Ag-NPs and ZnO-NPs within the same almond gum matrix. A total of 31 phytoconstituents of Prunus dulcis were screened for ADME properties via pkCSM, and potential bioactive compounds were docked against COX-2, TNF-α, and VEGFR-2. Quercetin-3-diglucoside and Corosolic acid recorded the strongest binding affinities toward COX-2 (- 8.8 kcal/mol), mechanistically supporting the anti-inflammatory basis of Prunus dulcis. The green-synthesized nanobiocomposites were characterized via UV-Vis spectroscopy, FTIR, XRD, SEM, zeta sizer, and zeta potential, with mean particle sizes of 73.33 nm and 225.2 nm for AG-Ag and AG-ZnO, respectively. In-vitro studies revealed strong antioxidant activity, with AG-ZnO exhibiting the highest TPC (342.29 ± 1.18 µg GAE/g) and TFC (158.20 ± 0.40 µg CE/g), and AG-P the lowest DPPH IC50 (47.67 ± 2.01 µg/mL). Both nanobiocomposites further demonstrated potent antibacterial and anti-biofilm activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Bacillus subtilis, alongside significant anti-inflammatory activity and negligible hemolytic toxicity. In vivo evaluation using a rabbit excisional wound model demonstrated superior wound contraction with AG-Ag (90%) and AG-ZnO (93%) compared to the standard drug Polyfax (68%) and untreated control groups. Treatment groups also showed significant modulation of inflammatory biomarkers (ESR, CRP, IL-6) at Days 7 and 15 compared to controls. Histopathological studies showed active collagen deposition, fibroblast migration, and keratinocyte proliferation. These findings collectively concluded Prunus dulcis gum-stabilized Ag/ZnO nanobiocomposites as safe, mechanistically validated, and biocompatible candidates for advanced wound healing therapeutics.