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CLINICAL STUDIES ON YERBA MATE-ILEX PARAGUARIENSIS

Fabelhafte Yerba Mate Wissenschaftler Team.


OUR MAIN RESULTS

Mate as a powerful in vitro inhibitor of LDL oxidation induced by putative oxidants in the artery wall It is now widely accepted that oxidative modification of LDL affects their metabolism leading to their accumulation in the arterial intima. Peroxynitrite is the product of the reaction between nitric oxide and superoxide, both of which are generated by macrophages. It is an oxidant which can also decompose to form the hydroxyl radical and nitrogen dioxide. In our study, simultaneous generation of nitric oxide and superoxide by the sydnonimine SIN-1 in the presence of LDL led to oxidation as measured by the accumulation of TBARS. Ip extracts were shown to inhibit this process in a dose dependent manner. These data indicate that the extracts contain substances that either bind peroxynitrite or quench NO and superoxide. In our experiments, inhibition of peroxynitrite-induced LDL oxidation did not go beyond 75% at concentrations in which it was above 95% in our previous studies when copper was the oxidant. This suggests that at least one component of the antioxidant properties of Ip is in fact a copper-chelating effect.

Lipoxygenase is enzymatically active on endogenous substrates in young human fatty streaks lesions and thus, may be of patho-physiological importance in early atherogenesis as supported by several lines of evidence, including studies on 15-lipoxygenase overexpression in the vessel wall. Modulation of lipoxygenase- induced lipid peroxidation might, therefore, constitute an important strategy to delay the development of atherosclerosis. When we incubated LDL in the presence of lipoxygenase and increasing concentrations of Ip extracts, we found dose dependent inhibition of the enzymatic-catalyzed oxidation. Our results are in agreement with previous data in the literature showing inhibition of lipoxygenase-induced LDL oxidation by individual flavonoid aglycones and glycosides.

In both oxidative systems employed, an effect is already significant at a concentration of the Ip extract of 2 µg/ml, which corresponds to a 1/500 dilution of the preparations usually drunk. At this point, we can only hypothesize as to whether there would be an in vivo effect and what its magnitude would be.

Mate does not induce DNA breaks in an eukaryotic system and protects DNA from hydrogen peroxide damage

Some flavonoids and crude herbal extracts have shown mutagenic activity, mainly in prokaryotes. On the other hand, some epidemiological data suggests that there may be a link between mate drinking and esophageal or oral cancer, although the injury is mainly thermal. In an effort to test a genotoxic effect of mate on eukaryotes we have shown that mate infusion did not induce double strand breaks (DSB) in our experimental conditions. Maximal DSB number was observed for H2O2 at a concentration of 10 mM both for haploid and diploid strains. Both mate infusion and alpha-tocopherol significantly decreased the DSB number, as well as the lethality induced by H2O2 . The DNA fragmentation induced by high concentrations of H2O2 is similar to that induced by high LET radiation.

Extensive clustered damage of this nature requires a high local concentration of radicals on DNA. Similar severity may result from the activation of H2O2 by transition metal ions located close to DNA. The Haber-Weiss reaction could be part of a general redox cycling process where Yap1p, thioredoxin, NADPH, GSH, and, in our case, phenol derivatives contained in "mate" infusion may act maintaining certain redox state and protecting different crucial targets involved in cell survival to oxidative stress. In fact, the nuclear export of Yap1p is specifically inhibited by H2O2, resulting in nuclear accumulation of this transcription factor and induction of its target genes.

Conclusion

Although rich in flavonoids, the ethnopharmacological uses of Ilex paraguariensis infusion both as a common drink or as a herbal preparation do not include atherosclerosis or cancer prevention. Our study confirms protection by Ip extracts of LDL oxidation generated by factors that may be involved in in vivo oxidation. Ip did not induce genotoxicity in a yeast model and protected DNA from hydrogen peroxide damage.

Relevant articles by the authors


Candreva EC, Keszenman DJ, Barrios E, Gelos U, Nunes E. Mutagenicity induced by hyperthermia, hot mate infusion, and hot caffeine in Saccharomyces cerevisiae. Cancer Res 1993 53(23):5750-3

Gugliucci A, Stahl AJ. Low density lipoprotein oxidation is inhibited by extracts of Ilex paraguariensis. Biochem Mol Biol Int. 1995;35(1):47-56.

Gugliucci A. Antioxidant effects of Ilex paraguariensis: induction of decreased oxidability of human LDL in vivo. Biochem Biophys Res Comm. 1996;224(2):338-44.

Gugliucci A, Menini T. The botanical extracts of Achyrocline satureoides and Ilex paraguariensis prevent methylglyoxal-induced inhibition of plasminogen and antithrombin III. Life Sci 2002 Dec 6;72(3):279-92

Other selected relevant articles

Schinella GR, Troiani G, Davila V, de Buschiazzo PM, Tournier HA. Antioxidant effects of an aqueous extract of Ilex paraguariensis. Biochem Biophys Res Comm.. 2000 269(2):357-60.

Fonseca CA, Otto SS, Paumgartten FJ, Leitao AC. Nontoxic, mutagenic, and clastogenic activities of Mate-Chimarrao (Ilex paraguariensis). J Environ Pathol Toxicol Oncol. 2000;19(4):333-46.

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Yerba Mate-Biochemistry-Alejandro


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