Impact of food-derived stilbenoids on the defensive response of dendritic cells to bacterial infection

Stilbenoids are a vast class of food-derived anti-inflammatory and antioxidant compounds, that include resveratrol. At difference with resveratrol, the action of most other stilbenoids is much less characterized, in particular for what attains the relationships occurring among chemical structure, antioxidant capacity, and their activity as inhibitors of specific enzymes or as potential regulators of complex pathways of cellular responses. Here we compared a number of monomeric and dimeric stilbenoids – obtained in sterically pure forms by chemical synthesis, as for their ability to modulate bacterially-induced cytokine production and the ROS-based defense response in bone marrow-derived dendritic cells. Despite having the highest chemical antioxidant activity, the two dimeric stilbenoids were weak inhibitors of LPS-induced ROS production in the cell system used in our studies, a response strongly inhibited by resveratrol and piceatannol. In summary, the anti-inflammatory and the antioxidant activity showed no straight relationship, and appeared related to several factors, such as the type of the pro-inflammatory signal, and the chemical structure and bioavailability of the stilbenoids. As for eliciting interleukin-based responses, all monomeric species - but none of the dimeric ones - showed dose-dependent inhibition of E. coli Nissle 1917 induced IL-12 and TNF-alpha, whereas only resveratrol and piceatannol inhibited IL-10 production. All monomers except trimethoxy-resveratrol inhibited IL-12, IL-10, and TNF-alfa production upon stimulation with L. acidophilus NCFM, while dehydro-delta-viniferin increased the IL-12 production. This comparative study shows that stilbenoids may affect cytokine production in ways trelated to the specific structure of the stilbenoid and to the type of microbial stimulation. Knowledge of how individual structures modulate the defense response may be exploited in future strategies for development on new drugs and nutraceuticals.