Computational Assessment of Synergistic Interactions Among Phytochemicals from Aloe vera, Plantago major, and Calendula officinalis for Wound Repair

Abstract

The integration of complementary and alternative medicine practices with modern computational and in silico approaches enables the reevaluation of ancient knowledge on a scientific basis. This paradigm facilitates biomolecular-level efficacy and safety assessments of traditional therapeutic methods, thereby strengthening their evidencebased use. In this way, herbal and natural remedies, considered part of cultural heritage, can be optimized through contemporary technologies and safely delivered to wider populations. Such a synthesis not only supports biomedical innovation but also ensures the sustainability of centuries-old healing 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 inflammationrelated protein target. These findings elucidate the interactions between plant-derived compounds and target proteins, thereby validating traditional uses through modern scientific methodologies and contributing to the development of novel therapeutic strategies.