Investigation of the antimicrobial, antibiofilm, and immunomodulatory activities of cranberry (Vaccinium macrocarpon L.) proanthocyanidins against multidrug-resistant pathogens
摘要
The increasing emergence of multidrug-resistant (MDR) pathogens poses a significant challenge to global healthcare, necessitating the development of alternative antimicrobial strategies. In the present study, cranberry extract was evaluated for its antimicrobial, antibiofilm, antioxidant, and anti-inflammatory activities against a panel of clinically relevant microorganisms, including Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). The extract demonstrated notable antimicrobial activity, with minimum inhibitory concentration (MIC) values ranging from 32 to 512 µg/mL, exhibiting relatively higher efficacy against Gram-positive bacteria. Significant antibiofilm activity was observed at sub-inhibitory concentrations, where cranberry extract reduced biofilm formation by up to 75–80% at 1/2 MIC and 50–65% at 1/4 MIC (p < 0.05) across tested isolates. Scanning electron microscopy (SEM) further supported these findings by revealing alterations in biofilm architecture following treatment. In addition, the extract exhibited strong antioxidant activity, achieving more than 85% free radical scavenging activity at higher concentrations. Cytotoxicity assessment revealed an IC50 of approximately 450–500 µg/mL, with selectivity indices indicating a favorable therapeutic window, particularly against Gram-positive bacteria. Furthermore, in vivo evaluation using an infection model demonstrated improved survival rates (> 90%) and significant reductions in pro-inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and cyclooxygenase-2 (COX-2), compared with untreated infected controls (p < 0.05). Collectively, these findings highlight the potential of cranberry extract as a multifunctional therapeutic agent with antimicrobial, antibiofilm, antioxidant, and anti-inflammatory properties. The observed efficacy against MDR pathogens suggests its potential application as a complementary or alternative strategy for the management of resistant infections.