Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Wound Healing Potential of Plant Secondary Metabolites: In Silico, In Vitro, and In Vivo Experiments

Version 1 : Received: 19 April 2023 / Approved: 20 April 2023 / Online: 20 April 2023 (07:42:54 CEST)

How to cite: Casadiego, O.; Macias, O.; García, L.; Sanabria, E.; Baay, G.; Mantilla, J.C.; Escobar, P. Wound Healing Potential of Plant Secondary Metabolites: In Silico, In Vitro, and In Vivo Experiments. Preprints 2023, 2023040619. https://doi.org/10.20944/preprints202304.0619.v1 Casadiego, O.; Macias, O.; García, L.; Sanabria, E.; Baay, G.; Mantilla, J.C.; Escobar, P. Wound Healing Potential of Plant Secondary Metabolites: In Silico, In Vitro, and In Vivo Experiments. Preprints 2023, 2023040619. https://doi.org/10.20944/preprints202304.0619.v1

Abstract

Dysregulation of the arsenal of cells, growth factors, cytokines, proteases, and proteins involved in wound healing (WH), could delay the healing process. Plants and plant-derived molecules (PDMs) have been used as medicines for skin wounds. This study aimed to select and evaluate the pro-healing capacity of PMDs. Thirty-three PDMs and 10 therapeutic targets (TTs) were chosen for molecular docking and PDMs: aristolochic acid (AA), α-copaene, selinenes, β-caryophyllene (BC), and BCoxide, and TTs: metalloproteinase (MMP) 3, MMP13, and tumor necrosis factor (TNF α) for molecular dynamics. The bests inhibitor was AA, but because of its toxicity, BC and BCoxide were chosen for evaluation in HaCat cells and BALB/c mice excisional model. Both compounds were not toxic, and higher percentages of lesion area closure (LAC) were induced by BC treatment (p<0.05). All mice healed; however, an initial delay of LAC was induced by 0.05, 0.1% BCoxide, 0.1% BC, and allantoin. At the end of treatment, lower numbers of mast cells, level of cellular infiltrates (except 1% BCoxide and 0.05, 0.5%BC), epidermal thickness tendency (except 0.1, 0.5% BCoxide), and higher values of SC-thickness, and collagen fibers only by 0.5% BC treatment compared with untreated control (p<0.05) were observed. Our results show that BC is a promising multitarget candidate for wound healing treatment and optimization campaigns.

Keywords

wound healing; natural compound; excisional mouse model; molecular docking; dynamic molecular; caryophyllene; cytokines; digital histology

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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