Avaliação dos efeitos toxicológicos in vitro e neuroprotetores in vivo do extrato hidroalcoólico das folhas e raízes do Yacon (Smallanthus sonchifolius)

Abstract

Yacon (Smallanthus sonchifolius) is a tuberous root originating in the Andes, which has aroused interest due to its medicinal properties. Popularly the root is consumed in natura and leaves in the form of tea for the treatment of diabetes and cholesterol disorder. However, little is known about other properties of this plant. Thus, the objective of this study was to evaluate the in vitro toxicity of the hydroalcoholic extracts of the leaves and roots of yacon, as well as the in vivo effect of these extracts on β-amyloid (Aβ) protein-induced neurotoxicity. The phytochemical profile of the leaf and root by high performance liquid chromatography was determined and the cell viability test, genotoxic and mutagenic activity in leukocyte culture at the concentrations of 1 μg/mL, 10 μg/mL, 50 μg/ml and 100 μg/ml; cytotoxicity and cell death by apoptosis in the 3T3 cell line (1 μg/mL, 10 μg/mL, 50 μg/mL, 100 μg/mL and 500 μg/mL). We also investigated the effects of yacon leaf and root supplementation on memory, oxidative status of the hippocampus and biochemical profile in a model of Alzheimer's disease (AD). The animals in the supplemented groups received the extract by gavage for 14 consecutive days, on the 15th day the animals underwent stereotactic surgery for intrahiplocal β-amyloid (Aβ) injection. The supplementation was maintained for another 10 days, until the behavioral tests were started. The object recognition memory (RO) test and behavioral tests were performed. Oxidative stress parameters were evaluated in the hippocampus through classical methodologies. Biochemical parameters were analyzed in serum by automated equipment. The main compounds found in the roots and leaves were the flavonoids quercetin and apigenin, respectively. No mutagenic or cytotoxic activity was observed in the leukocyte culture, and the genotoxic potential was observed at the highest doses of leaf extract (50 and 100 μg/mL) and roots (100 μg/mL). The highest concentrations of yacon leaf extract (50, 100 and 500 μg/mL) showed cytotoxic activity and all concentrations induced apoptosis in 3T3 cells. Biochemical markers showed no difference between groups, except for glucose levels that were significantly lower in non-supplemented animals and submitted to intra-postoperative Aβ injection. Leaf and root reduced oxidative stress in the hippocampus, but only supplementation with the yacon leaf extract prevented the Aβ-induced memory deficit in the short- and long-term memory test. These results suggest that yacon is rich in phenolic compounds and, at high doses, may present a toxic potential. We hypothesize that the in vivo effects are due to the higher concentration of the apigenin phytochemical compound in the yacon leaves, since recent studies indicate that this compound has an important neuroprotective effect. Therefore, this study demonstrates the yacon leaves as a candidate for future use in the prevention and / or treatment of AD.