Resveratrol-Derived Dimers With Antimicrobial and Immune-Enhancing Activities

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.