Bioactive goldenseal (Hydrastis canadensis) fraction suppresses multidrug-resistant Pseudomonas aeruginosa in a rat burn wound model: oral and topical administration

Abstract

Multidrug-resistant (MDR) Pseudomonas aeruginosa is a prominent pathogen implicated in burn wound infections, creating substantial therapeutic obstacles due to its antibiotic resistance and enhanced virulence mediated by quorum sensing (QS). This study explored the anti-infective and wound-healing properties of a standardized extract from Hydrastis canadensis (Goldenseal; GS) using integrated in silico, in vitro, and in vivo approaches. LC-ESI-MS/MS profiling identified 52 phytochemicals, including alkaloids, flavonoids, phenolic acids, and glycosides, in the extract. Molecular docking against QS regulators (LasR, LasI, RhlR, and RhlI) revealed preferential binding to LasR, with naringenin-7-O-glucoside showing the highest affinity and chlorogenic and orotic acids exhibiting selective interactions. In vitro, GS demonstrated antibacterial activity (MIC = 3.125 mg/mL), significantly inhibited biofilm formation, and reduced lasR and rhlR expression by 95.3% and 84.8%, respectively (p < 0.001). In a rat model of second-degree burns, both oral and topical GS administration was evaluated in vivo, revealing enhanced wound contraction, increased collagen deposition, and improved histopathological outcomes. These outcomes were linked to a reduction in TNF-α and IL-1β levels, alongside an increase in VEGF and bFGF levels, as well as the upregulation of antimicrobial peptides, including CAMP and RBD2. Moreover, the efficacy of topical application surpassed that of oral administration. These findings indicate that GS suppresses QS-regulated virulence and promotes wound repair, supporting its potential application as an adjunctive therapeutic approach for burn wound infections caused by MDR P. aeruginosa.