This study investigated the anti-inflammatory action of cyanidin-3-glucoside (Cy3glc), an anthocyanin widely spread in diet, in comparison and in association with 5-aminosalicylic acid (5-ASA), an anti-inflammatory reference drug for ulcerative colitis. The efficacy, action mechanism and interaction between Cy3glc and 5-ASA were assessed in vitro, in an LPS-activated macrophage cell line. Our data showed a higher effectiveness of Cy3glc in counteracting inflammatory mediators as compared to 5-ASA at the same concentration. In addition, the mixture afforded a better protection than Cy3glc and a much better than 5-ASA, showing a synergistic effect in terms of reducing NO and ROS cellular production. Although neither Cy3glc nor the mixture counteracted LPS-induced NF-κB activation, the mixture strongly inhibited AP-1 translocation to the nucleus and prevented p38 MAPK and JNK phosphorylation suggesting that, the co-administration of a biologically active food ingredient and a medicine could be a potential strategy to increase the medicine therapeutic effect.