Integrative network pharmacology and experimental validation of rubus ulmifolius leaf extract in a rat model of MRSA-infected wounds.

Abstract

BACKGROUND/OBJECTIVES: Wounds and burn injuries are major global health challenges, often exacerbated by methicillin-resistant Staphylococcus aureus (MRSA) infections. This study investigated the wound-healing efficacy of Rubus ulmifolius (RU) leaf extract, which contains bioactive compounds including rutin, vanillic acid, syringic acid, gallic acid, and protocatechuic acid. Network pharmacology analysis identified interactions between these compounds and key inflammatory and antibacterial targets, notably TNF-α and IL-1β, suggesting a role in modulating MRSA-associated inflammation. METHODS: Antibacterial activity of RU extract was confirmed against MRSA strains. RU-based topical creams (0.5% and 1%) were applied to MRSA-infected excisional wounds in albino rats for 14 days. Wound closure was evaluated on days 0, 3, 7, and 14. RESULTS: RU cream (1%) significantly enhanced wound contraction (98%) compared with the untreated control group (62%). The Fucidincream-treated (positive control) and RU 0.5% groups showed comparable wound closure rates of 89% and 88%, respectively. ELISA analysis revealed that RU treatment reduced TNF-α and IL-1β levels while increasing IL-10, VEGF, PDGF, and RUNX-2 expression. Histopathological examination demonstrated enhanced granulation tissue formation, reduced inflammation, and improved re-epithelialization and collagen maturation in the RU-treated groups, exceeding the healing quality observed with the reference drug, Fucidin. CONCLUSIONS: RU extract accelerates wound healing by modulating inflammatory responses and promoting tissue regeneration. RU extract demonstrated beneficial effects on MRSA-infected wound healing in rats, suggesting its potential as an adjunct therapy warranting further preclinical and clinical validation, warranting further clinical evaluation.