Yerba mate tea ( Ilex paraguariensis ) is growing in popularity around the world. The objective of this study was to investigate the potential anti-inflammatory effect of yerba mate tea (MT) extracts as well as some of its phytochemicals and their interactions. MT and decaffeinated MT extracts [1-300 microM chlorogenic acid (CHA) equiv]; CHA, caffeine from MT (matein), and mate saponins (1-300 microM); quercetin (1-200 microM); and ursolic and oleanolic acids (1-100 microM) were tested by measuring their ability to inhibit COX-2/PGE(2) and iNOS/NO pathways in LPS-induced RAW 264.7 macrophages. Mate saponins (IC(50) = 20 microM) and oleanolic acid (IC(50) = 80 microM) significantly inhibited iNOS/NO pathways, whereas ursolic acid showed low or no inhibition at 100 microM. Quercetin was the most potent inhibitor of pro-inflammatory responses at a concentration 10 times lower than the concentrations used of other compounds (IC(50) = 11.6 microM for NO, 7.9 microM for iNOS, and 6.5 microM for PGE(2)). Combination of quercetin/mate saponins (0.001:0.004, molar ratio) resulted in synergistic interaction inhibiting both NO and PGE(2) production. It also suppressed IL-6 and IL-1beta production and resulted in reduction of LPS-induced nuclear translocation of nuclear factor-kappaB subunits. MT extract did not have a potent anti-inflammatory effect perhaps due to the antagonistic effect of some of its compounds. However, whole MT consumption still has a promising anti-inflammatory outcome mainly through the PGE(2)/COX-2 pathway. To the authors' knowledge, this is the first study demonstrating the efficacy, interactions, and mechanisms of some MT phytochemicals in inhibiting pro-inflammatory responses.