Saponins in Yerba Mate Tea (Ilex paraguariensis A. St.-Hil) and Quercetin Synergistically Inhibit iNOS and COX-2 in Lipopolysaccharide-Induced Macrophages through NFκB Pathways

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 mu M chlorogenic acid (CHA) equiv]; CHA, caffeine from MT (matein), and mate saponins (1-300 mu M); quercetin (1-200 mu M); and ursolic and oleanolic acids (1-100 mu M) 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 (IC50 = 20 mu M) and oleanolic acid (IC50 = 80 mu M) significantly inhibited iNOS/NO pathways, whereas ursolic acid showed low or no inhibition at 100 mu M. Quercetin was the most potent inhibitor of pro-inflammatory responses at a concentration 10 times lower than the concentrations used of other compounds (IC50=11.6 mu M for NO, 7.9 mu M for iNOS, and 6.5 mu M for PGE(2)). Combination of quercetin/mate saponins (0.001:0.004, molar ratio) resulted in synergistic interaction inhibiting both NO and PGE2 production. It also suppressed IL-6 and IL-1 beta production and resulted in reduction of LPS-induced nuclear translocation of nuclear factor-kappa B 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.