In Silico Evaluation of Wound-Healing Phytochemicals from Pistacia Lentiscus and Rosmarinus Officinalis

Abstract

Wound healing is a complex biological process involving inflammation, oxidative-stress regulation, angiogenesis, extracellular-matrix (ECM) remodeling, cell migration, and tissue regeneration. Pistacia lentiscus L. and Rosmarinus officinalis L. are traditional Mediterranean medicinal plants widely recognized for their antioxidant, anti-inflammatory, antimicrobial, and wound-related properties. The present study employed an integrated computational workflow to investigate the potential wound-healing mechanisms of phytochemicals derived from both species. Selected phytochemicals were evaluated against eight wound-healing related protein targets, including cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), Kelch-like ECH-associated protein 1 (Keap1), vascular endothelial growth factor receptor-2 (VEGFR-2), matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9), transforming growth factor-beta receptor I (TGF-βRI), and focal adhesion kinase (FAK). Molecular docking, interaction mapping, ADME prediction, toxicity assessment, and multi-criteria ranking were integrated into a unified candidate-prioritization framework. Carnosic acid demonstrated the strongest predicted interaction with COX-2 (−9.2 kcal/mol), rosmarinic acid exhibited favorable interactions with MMP-9 and MMP-2, quercetin showed high affinity toward VEGFR-2, and myricetin demonstrated promising interactions with Keap1. The results support a multi-target pharmacological model in which phytochemicals may contribute to wound repair through complementary modulation of inflammatory signaling, oxidative-stress regulation, angiogenesis, extracellular-matrix remodeling, and tissue regeneration. These findings constitute computationally generated mechanistic hypotheses requiring experimental validation.