Avaliação do potencial farmacológico do extrato aquoso das folhas de Acrocomia aculeata (Jacq.) Lodd ex. Mart

Abstract

The increase in life expectancy of the world population is directly related to the incidence of chronic diseases such as neurodegenerative and cardiovascular diseases, rheumatoid arthritis, diabetes, cancer, among others. The impact of the treatment of these diseases and the maintenance of health represents a high economic and social costs. Oxidative stress is a key factor associated with the etiology and progression of these diseases. Thus, the development of therapeutic alternatives is of fundamental importance, especially with low cost, easy access, and, above all, with relevant pharmacological potential. Medicinal plants, especially those with antioxidant potential, are an important source of natural compounds that can be used as raw materials in the development of new therapies. Acrocomia aculeata is a palm native of Brazil, whose leaves are rich in phenolic and flavonoid compounds, with a proven antioxidant effects. Thus, our objective was to evaluate the effect of the aqueous extract of A. aculeata leaves (EAAa) in two conditions related to oxidative stress, the complications associated with diabetes and the cardiotoxicity induced by chemotherapy with doxorubicin (Dox). For the investigation of the effects associated with diabetes complications, normoglycemic Wistar rats and non-obese type 2 diabetic rats, Goto-Kakizaki (GK), were treated daily with 200 mg.kg-1 EA-Aa for 30 days and evaluated in relation to the anthropometric and biochemical parameters. After treatment, the animals were anesthetized and euthanized. Proteins associated with hyperglycemia and oxidative stress were evaluated in target organs, in 3T3-L1 pre-adipocytes, and in dermal microvascular cells (HMVec-D) induced by H2O2 to redox imbalance. The results showed that EA-Aa reduced fasting glycemia and triglycerides of diabetic rats, by increasing the levels of proteins such as GLUT-4, PPARγ and AMPK and reduced oxidative stress in 3T3- L1 pre-adipocytes and HMVec-D cells, in addition to promoting higher levels of proteins related to stress resistance, SIRT1 and NRF2. Regarding the effects of EA-Aa in association with Dox, a chemotherapeutic agent known for its high cardiotoxicity caused by oxidative stress, in vitro experimental models were used: normal cells (PBMC peripheral blood cells and H9c2 cardiomyoblasts) and tumor cells (K562 erythroleukemics) and breast cancer MCF-7), and in vivo, C57Bl/6 mice, treated with EA-Aa, with or without Dox. EA-Aa showed no toxicity in normal cells in vitro and in the acute oral toxicity test in vivo. Regarding the effect of EA-Aa associated with Dox, there was a reduction in oxidative stress induced in erythrocytes, in H9c2 cells and in cardiotoxicity in C57Bl 6 mice, in addition to potentiating the cytotoxic effect of Dox in tumor cells. Together, our results show the antioxidant protection of EA-Aa in diabetic complications and in those resulting from treatment with Dox in various tissues, as well as its mechanisms of action. Thus, the data presented here support new studies based on the pharmacological potential of EA-Aa and its phytochemicals for the development of therapeutic strategies for the treatment of both conditions.