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.