Wound-Healing Efficacy of Garcinia pedunculata Fruit Extract: In Vivo and In Silico Validation of Regenerative Mechanisms With Histological Analysis

Abstract

Garcinia pedunculata Roxb., traditionally used for treating inflammation and infections, remains underexplored for its wound-healing potential. This study evaluated the wound-healing efficacy of the G. pedunculata fruit ethanolic extract (GP-EE) using in vivo and in silico approaches. Phytochemical profiling of GP-EE was performed via Gas Chromatography–Mass Spectrometry (GC–MS). GP-EE was formulated into 5% and 10% ointments and evaluated in excision and burn wound models in Wistar rats, using 0.2% nitrofurazone as a standard. Wound contraction, epithelialization period, and histopathological features were assessed. Molecular docking was used to examine the interactions of identified bioactives with wound-healing targets TGF-β receptor type 1 and IL-1β, and ADMET properties were evaluated through in silico analysis. GC–MS identified eight major compounds, including mandelic acid (15.05%), gallic acid (7.58%), ellagic acid (4.36%), quercetin (3.45%), and ascorbic acid (4.71%). The 10% GP-EE ointment showed complete wound closure by day 17 in excision and by day 21 in burn models, significantly faster than the control (p < 0.001). Epithelialization time significantly decreased from 20.5 ± 0.8 to 17.33 ± 0.42 days in excision and from 20.24 ± 1.76 to 16.5 ± 0.66 days in burn wounds after 10% GP-EE treatment (p < 0.001). Histology revealed increased fibroblast proliferation, dense collagen deposition, and moderate neovascularization. Molecular docking showed that quercetin and ellagic acid exhibited strong binding affinities for TGF-βR1 (−9.3 kcal/mol) and IL-1β (−6.3 kcal/mol), comparable to mefenamic acid. The synergistic antioxidant, anti-inflammatory, and collagen-promoting activities of GP-EE accelerate wound contraction and tissue regeneration. These findings validate the traditional use of G. pedunculata and suggest that GP-EE is a promising natural candidate for the development of phytotherapeutic wound-healing formulations.