Potential wound healing effects of Combretum aculeatum Vent. aerial parts; FOXO1/MIP2 modulation supported by LC-QTOF-MS/MS and molecular docking approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Combretum aculeatum, widely distributed in Sudan and South Darfur, has been traditionally used for wound healing.

AIM OF THE STUDY: This study aimed to investigate the wound healing effect of the ethanolic extract of C. aculeatum aerial parts in a mice model, using Mebo® as a reference standard.

MATERIAL AND

METHODS

The total extract (2.5% and 5%) was applied topically to assess its potential for wound healing activity in mice wound model. Several markers were analyzed (collagen type I, Glutathione (GSH), Forkhead box protein O1 (FOXO1), Macrophage inflammatory protein 2 (MIP2), and Malondialdehyde (MDA) levels alongside histopathological assessment. Consequently, the extract was characterized using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). Molecular docking and dynamic studies of tentatively identified metabolites were also performed.

RESULTS

Topical treatment with C. aculeatum extract (2.5% and 5% w/w) was associated with increased levels of collagen type I, GSH, FOXO1, and MIP2, alongside a significant reduction in skin MDA content. Histopathological analysis showed improved skin architecture, characterized by enhanced re-epithelialization and extracellular matrix deposition, which coincided with the modulation of oxidative stress and inflammatory biomarkers. LC-MS/MS profiling identified fifty-seven metabolites in the ethanolic extract for the first time. In silico modeling of tentatively identified tannins and terpenes suggested that Eschweilenol C possesses high binding affinity for the catalytic sites of Keap1 and TNF-α receptors, as supported by molecular dynamics simulations and MM/PBSA or MM/GBSA calculations.

CONCLUSIONS

This study showed that C. aculeatum aerial parts are a promising therapeutic candidate in accelerating wound healing.