Resveratrol‐Derived Dimers With Antimicrobial and Immune‐Enhancing Activities

ABSTRACT

In search for novel antibiotic candidates, polyphenols represent an unexploited source with a nearly inexhaustible number of promising compounds. In addition to the antimicrobial activity, some polyphenols modulate the immune response in a way that could enhance the clearance of invading pathogens. This study investigated four resveratrol‐derived dimeric compounds, dehydro‐δ‐viniferin, (±)‐ trans ‐δ‐viniferin, viniferifuran, and (±)‐ε‐viniferin, for their antimicrobial activity against methicillin‐resistant S. aureus . In addition, their immunomodulating properties in bacterially challenged dendritic cells were assessed. We identified dehydro‐δ‐viniferin as exhibiting the most potent antimicrobial activity against methicillin‐resistant Staphylococcus aureus with a minimal inhibitory concentration of 2 μg/mL and a minimal bactericidal concentration of 8 μg/mL, respectively. Furthermore, dehydro‐δ‐viniferin showed significant enhancement of the S. aureus ‐induced IL‐12 production from bone marrow‐derived dendritic cells, which could be ascribed to a decrease in the production of IL‐10. Only if dehydro‐δ‐viniferin was administered to dendritic cells prior to bacterial stimulation, IL‐12 production was increased; if added later, the increase in IL‐12 was lost although the IL‐10 production was reduced. This suggests that dehydro‐δ‐viniferin interferes with the signaling pathway leading to IL‐10, which in turn influences the IL‐12 production in a time dependent manner. Collectively, dehydro‐δ‐viniferin is a potent antimicrobial against methicillin‐resistant S. aureus with enhancing effects on the bacterially induced IL‐12 response in antigen‐presenting cells. We therefore suggest dehydro‐δ‐viniferin as a promising antibiotic candidate against multidrug‐resistant Gram‐positive bacteria.