In Silico Evaluation of Synergistic Phytochemical Interactions for Wound Repair

Abstract

The integration of complementary medicine with modern computational and in silico approaches enables the scientific re-evaluation of traditional knowledge, particularly highlighting the role of terpenes in herbal remedies. This paradigm facilitates biomolecular-level assessment of efficacy and safety, strengthening the evidence-based use of plant-derived compounds in wound healing. Through such approaches, natural remedies can be optimized and safely delivered to wider populations, supporting both biomedical innovation and the sustainability of traditional therapeutic knowledge. The present study aims to investigate, at the molecular level, the combined use and potential synergistic effects of Calendula officinalis, Plantago major, and Aloe vera, which have been traditionally employed in wound treatment. In this context, molecular docking interactions, synergy scores, ADMET properties, and molecular dynamics simulations were evaluated for three major terpenes from C. officinalis essential oil and three major alkaloids reported in the ethanolic extracts of P. major and A. vera. The results revealed that, in addition to the high inhibitory activity of alkaloid constituents against inflammatory and microbial targets, the combination of aloe-emodin, plantamajoside, and τ-muurolol exhibited a pronounced molecular synergy against the T204D inflammation-related protein target. These synergistic interactions among the phytochemicals indicate enhanced wound healing potential, providing a scientific basis for future plant-based therapeutic strategies in clinical wound care.