Propriedades antiateroscleróticas da fração butanólica de Ilex paraguariensis A. St.-Hil. em coelhos hipercolesterolêmicos

Abstract

Atherosclerosis is a disease characterized by a chronic inflammatory process resulting primarily from an endothelial dysfunction and consequent formation of atheromatous plaques that cause a narrowing of arteries and may lead to its occlusions, causing myocardial infarction, stroke, pulmonary embolism and even death of the individual. Currently the drug treatment of dyslipidemias mainly include lipid-lowering drugs such as statins. However, there is a high interest in obtaining new drugs and treatment models because of the adverse effects these drugs present. Consequently, the population's interest in plants and plant extracts with potential cardioprotective effect has increased. Phytotherapics are a good alternative to synthetic drugs due to the lower cost of treatment, less reporting of adverse effects and also, for many herbal products, show similar efficacy to synthetic ones. Considering that the extract of Ilex paraguariensis A. St.-Hil. (Aquifoliaceae) is rich in phenolic compounds and has a proven lipolipidemic action and other cardioprotective effects by acting to inhibit lipid peroxidation in Wistar rats, we aimed to analyze the effects and regression of atherosclerosis in New Zealand rabbits submitted to an atherogenic diet (commercial cholesterol plus 1% cholesterol) for 8 experimental weeks. This method allowed the formation of atherosclerotic lesions in the thoracic and abdominal aortas. From the fourth week of the atherogenic diet, the butanolic fraction of Ilex paraguariensis (n-BFIP) was administered daily at 10, 30 and 100 mg/kg doses per gavage. Control animals received simvastatin (5 mg/kg) or vehicle (filtered water) by the oral route. Dosages of the lipid profile of the animals were performed on days 0, 30 and 60 after the start of the experiment. At the end of the experimental period, the rabbits were submitted to euthanasia and later, their thoracic and abdominal arteries were removed for evaluation of the atherogenic profile. Macroscopic and microscopic analysis revealed that the extract inhibited atherogenesis in rabbit arteries with dose-dependent results. The 100 mg/kg group had a better inhibition of atheromatous plaque formation and their results were comparable to those in the simvastatin group. Despite its visible effects on atheroprotection, n-BFIP did not significantly alter serum lipid levels during treatment, however, its antiatherosclerotic effects are estimated to be due to antioxidant and anti-inflammatory effects since the fraction demonstrated the ability to interleukin-1β (IL-1β), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) that modulate the inflammatory response in vessels. The results of this research may influence the scientific community in the interest of I. paraguariensis and its respective butanolic fraction in obtaining new herbal products and in the study of its active components for prophylactic purposes or in the treatment of dyslipidemias and atherosclerosis.