Metabolite profiling and molecular docking insights into the wound healing efficacy of Pelargonium zonale in a rat burn model

Abstract

Pelargonium zonale has a long history of use in traditional medicine for wound healing, supported by scientific evidence of its topical, hemostatic, and antibacterial properties. The current study aims to comprehensively investigate the wound healing potential and phytochemical profiling of P. zonale leaves hydroacetone extract (PZLHAE) and to provide insight into its binding affinity to wound healing targets using an in silico approach. The chemical composition was putatively examined utilizing High-performance liquid chromatography coupled with high-resolution electrospray ionization/tandem mass spectrometry (HPLC HRESI-MS/MS). The wound healing potential of PZLHAE was assessed using 24 healthy adult male Sprague-Dawley rats randomly divided into four groups comprising 6 rats each after induction of burn: normal control group (receiving no wound) (I), positive (burn) control group (II), 2% fusidic acid (Fucidin ointment) standard treated group (III), and 2% PZLHAE gel treated group (IV). All rats subjected to skin biopsy were included in the histological examination. The compound interactions with glycogen synthase kinase-3 beta (GSK-3 β ) were examined using molecular docking. The study demonstrated that PZLHAE gel considerably accelerated wound healing. By day 14, the wound area in the extract-loaded gel-treated group was reduced to 11.03 mm 2 , a superior outcome compared to both the burn control (17.04 mm 2 ) and the fusidic acid ointment standard (13.00 mm 2 ). Histopathological examination confirmed these findings, showing that PZLHAE-loaded gel treatment resulted in a well-healed burn wound with macroscopic remodeling and restoration of normal dermal tissues, skin function, and morphology, in contrast to the disorganized fibrosis observed in the fusidic acid ointment-treated and control groups. Using LC HRESI-MS/MS, 37 metabolites, mainly flavonoids, phenolic acids, and gallotannins, were identified. Several compounds were identified as putative ligands with high predicted binding affinities toward GSK-3 β using exploratory molecular docking, with rutin and peltatoside showing high-binding affinities with values of −9.5 and −9.3 kcal/mol, respectively, suggesting a predicted interaction with GSK-3 β that may influence downstream inflammation and cellular proliferation pathways. These findings demonstrate the potential of P. zonale as a promising source for developing new natural product-based therapies for burn wound treatment.