Orientadora: Profa. Dra. Rosane Marina Peralta

Data da Defesa: 17/12/2020


INTRODUCTION AND AIMS: The yerba mate or mate (YM) (Ilex paraguariensis A. St. Hil.) is a plant native from Paraguay, Uruguay, Argentina and Brazil. The powder of YM leaves and thin stems are used for the preparation of several stimulant drinks. The three most important are chimarrão (hot water extract of green dried leaves), tererê (cold water extract of green dried leaves) and mate tea (hot water extract of toasted leaves). Yerba mate is known to be rich in phenolic acids such as caffeic acid and chlorogenic acid and their derivatives and flavan-3-ols. Due to this, its consumption has been considered beneficial for health and different bioactive properties have been reported. The health properties of YM are multivariate. They may encompass effects on metabolism and metabolism-derived disturbances, but they may also manifest themselves in the realm of oxidative stress and inflammation. The present work represents an attempt of approaching both types of actions. The actions of YM on metabolism-derived disturbances are displayed in a bibliographic review which analyzes the main findings related to the treatment of diabetes, obesity and metabolic syndrome. The actions on oxidative stress and inflammation, in turn, are analyzed experimentally in terms of the effects of a continuous and regular administration of yerba mate infusions to adjuvant-induced arthritic rats. The latter represents a suitable model for individuals who suffer or are predisposed to rheumatoid arthritis.
MATERIAL AND METHODS: For the review work, the specialized literature was searched for studies that used yerba mate to treat diabetes, obesity and/or metabolic syndrome. The selected works were evaluated according to the type of research and classified as: in vitro, in vivo in animals and in vivo in humans. For the second work, an experimental study, yerba mate was obtained from commercial sources in southern Brazil. First, an extract was prepared in the same way as the beverage “chimarrão”, which is consumed in Brazil. For the preparation, 1.5 L of water at 80 ºC were added to 85 g of yerba mate. After 5 minutes, the mixture was filtered in a vacuum pump. The extract was lyophilized and kept at -20 ºC until use. The animals used in the study were fed ad libitum with a standard laboratory diet and kept in standard laboratory conditions. Freund's complete adjuvant (Mycobacterium tuberculosis inactivated by heat, derived from the human strain H37Rv), suspended in mineral oil, was used to induce arthritis. All procedures were previously approved by the Ethics Committee on Animal Experimentation at the State University of Maringá (Protocol No. 6168170117). The animals were divided into 7 groups: (1) group C were healthy animals (controls); (2) the C-T 400 group were healthy animals treated with 400 mg/kg of Ilex paraguariensis extract (yerba mate); (3) the C-T 800 group were healthy animals treated with 800 mg/kg of yerba mate extract; (4) the AIA group was the arthritic rats; (5) the AIA-T 400 group included arthritic rats treated with 400 mg/kg of yerba mate extract; (6) the AIA-T 800 group comprised arthritic rats treated with 800 mg/kg of yerba mate extract; (7) AIA-ibuprofen group were arthritic rats treated with ibuprofen (35 mg/kg, positive controls). During the treatment period, the appearance of secondary lesions and the evolution of edema of the hind legs were evaluated. On the 18th day after arthritis induction, the animals were euthanized and blood, brain, and liver were collected for analysis. Reactive oxygen species (ROS), GSH and GSSG, antioxidant enzymes, TBARS and carbonylated proteins in the brain and liver were quantified. In plasma the reduction power of iron ions, the levels of carbonylated proteins and thiol groups and the myeloperoxidase activities were quantified. Levels of albumin, globulins, and ALT and AST activities were also measured in blood plasma in order to check for liver and kidney damage. Finally, the poly- and mononuclear leukocytes in the synovial fluid of the femorotibial cavity of the knee were counted.
RESULTS AND DISCUSSION: According to in vitro studies, yerba mate can act as an anti-obesity agent in two main ways: by inhibiting the pancreatic lipase enzyme and by regulating genes related to adipogenesis. Regarding the antidiabetic effects, some studies have shown that the extract of yerba mate, as well as its main phenolic constituents, have an anti-glycation effect and are capable of inhibiting the activity of disaccharidases. This is important because glycation agents are linked to various inflammatory complications in the body, being the basis of insulin resistance, metabolic syndrome and others. In addition, by inhibiting the enzymatic hydrolysis of some carbohydrates, blood glucose bursts can be delayed after meals, preventing glycemic spikes. Animal studies indicate that the consumption of yerba mate actually promotes improvements in body profile, biochemical parameters and regulates the expression of genes implicated in diabetes and obesity. Regarding studies in humans, few studies have evaluated the effects of mate as an adjunct in the treatment of diabetes, obesity and metabolic syndrome. Some clinical studies have shown that the intake of yerba mate derivatives was able to decrease serum fasting blood glucose levels and serum glycated hemoglobin levels. The consumption also improved body lipid composition, decreased body fat and improved waist-to-hip ratio. Our experimental study on the effects of the yerba mate extract on the modifications caused by rheumatoid arthritis induced by adjuvant in rats revealed multiple beneficial effects. It was found that the yerba mate extract caused decreases in ROS levels and in oxidative damage to proteins and lipids. It also increased the plasma antioxidant capacity, the GSH levels and the GSH/GSSH ratio in both liver and brain. In addition, the treatment reversed the modified activities of xanthine oxidase and superoxide dismutase in the liver and brain, while a similar action on catalase was found only in the brain. Possibly, the anti-inflammatory actions of the constituents of yerba mate (for example, the group of chlorogenic acids) are the primary events that produce most of these beneficial effects. The direct elimination of reactive oxygen species (ROS), however, can also play a significant role, as inflammation and the production of ROS are interdependent phenomena capable of influencing each other.
CONCLUSIONS: Review of the pertinent literature reveals that there are still gaps regarding the understanding of the mechanisms by which the yerba mate extracts act on chronic diseases such as diabetes and metabolic syndrome. Further studies are thus necessary in order to establish not only the effectiveness but also the mode of action of yerba mate. Studies in humans will be especially useful in this area. Regarding the treatment of adjuvant-induced rheumatoid arthritis, the administration of yerba mate was clearly beneficial, reducing both inflammation and oxidative stress. It is possible that the anti-inflammatory actions of the constituents of yerba mate are the main events that produce these beneficial effects. However, the ability to scavenge free radicals can also help to protect against inflammation. In principle, the same can be expected for patients suffering from rheumatoid arthritis, due to the similarities between the disease in humans and the adjuvant-induced disease in rats. In addition, other inflammatory diseases may have their symptoms mitigated by the continuous daily intake of traditional yerba mate drinks.
Key words: yerba mate, Ilex paraguariensis, chronic diseases, diabetes, obesity, rheumatoid arthritis.


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