Opuntia ficus-indica Leaves Extract-Derived Topical Cream for Burn Healing: In Vivo, In Vitro, and In Silico Studies

Burn injuries remain a significant global health challenge, often complicated by delayed tissue regeneration, microbial infection, and dysregulated inflammatory responses, thereby necessitating the development of safe and multifunctional therapeutic strategies. In the present study, a topical formulation based on Opuntia ficus-indica (OFI) leaf extract was developed and comprehensively evaluated for burn wound healing through integrated phytochemical characterization, biological assessment, and computational modelling. LC–MS profiling revealed ferulic acid, catechin, myricetin-3′-rhamnoside, and quercetin-3-arabinoside as the predominant bioactive constituents. The extract demonstrated pronounced antioxidant activity (DPPH IC₅₀ = 432.42 µg/mL), significant anti-inflammatory potential (IC₅₀ = 629.71 µg/mL), mild antibacterial efficacy, and measurable photoprotective capacity (SPF = 8.34) in vitro. Topical creams containing 5%, 10%, and 20% OFI extract were successfully formulated, exhibiting physicochemical stability, biocompatibility, and absence of dermal irritation. In vivo burn wound experiments in a rat model revealed that the 10.0% OFI formulation achieved approximately 90% wound contraction by day 21, surpassing the healing efficacy of Vaseline® (65%) and MEBO® (85%). Hematological parameters indicated restoration toward physiological homeostasis, while histopathological analysis confirmed accelerated re-epithelialization, well-organized collagen deposition, enhanced dermal remodeling, and reduced inflammatory cell infiltration. Molecular docking analyses further demonstrated favorable binding affinities of OFI phytoconstituents toward key molecular targets implicated in inflammation and tissue remodeling, including COX-1, COX-2, MMP-9, and TNF-α, providing mechanistic support for the observed therapeutic outcomes. These findings highlight OFI leaf extract as a promising multifunctional bioactive platform for burn wound management, with substantial translational potential for advanced therapeutic development.