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 μM chlorogenic acid (CHA) equiv]; CHA, caffeine from MT (matein), and mate saponins (1-300 μM); quercetin (1-200 μM); and ursolic and oleanolic acids (1-100 μM) were tested by measuring their ability to inhibit COX-2/PGE ₂ and iNOS/NO pathways in tPS-induced RAW 264.7 macrophages. Mate saponins (IC₅₀ = 20 μM) and oleanolic acid (IC₅₀ = 80 μM) significantly inhibited iNOS/NO pathways, whereas ursolic acid showed low or no inhibition at 100 μM. 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 μM for NO, 7.9 μM for iNOS, and 6.5 μM for PGE₂). Combination of quercetin/mate saponins (0.001:0.004, molar ratio) resulted in synergistic interaction inhibiting both NO and PGE₂ production. It also suppressed It-6 and It-1β production and resulted in reduction of tPS-induced nuclear translocation of nuclear factor-κB 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.