Composicao fitoquimica e investigacao da farmacodinamica do extrato aquoso da Campomanesia xanthocarpa sobre o sistema cardiovascular em ratos

Abstract

Cardiovascular diseases are the leading cause of death in Brazil and are strongly associated with metabolic disorders such as the metabolic syndrome. Metabolic syndrome is characterized by the co-occurrence of cardiovascular risk factors such as hypertension, hyperinsulinemia, glucose intolerance, central obesity and dyslipidemia. Campomanesia xanthocarpa, known in Brazil as Guabiroba, has been used empirically because of its potential effects on reduce blood cholesterol levels, and for various conditions including inflammatory, renal, digestive, dyslipidemia, and other diseases. The objective of this study was to analyze the chemical composition and to investigate the effects of the aqueous extract of C. xanthocarpa on blood pressure of normotensive rats acutely, as well as its possible mechanism of action, using in vivo and in silico procedures. In addition, the effects of C. xanthocarpa aqueous extract on myosin ATPase activity and gene expression of cardiac markers in rats with metabolic syndrome induced by a high fructose diet were also evaluated. The extract was evaluated for total phenolic compounds and total flavonoid content. The chemical components were determined by HPLC analysis. For acute evaluation, systolic and diastolic blood pressure and heart rate were measured in the presence of extract and with drug administration. For the evaluation of animals with metabolic syndrome, the animals were treated for 30 days with aqueous extract of the leaves prepared by infusion. Cardiac myosin extraction was performed with high ionic strength centrifugation, the myosin ATPase activity measurement was quantified by the ionorganic phosphate released through a colorimetric method and expressed in nmolPi/min/mg of protein. Gene expression of α-MHC, β-MHC, atrial natriuretic factor and skeletal α-actin was evaluated by real-time PCR. C. xanthocarpa leaves presented a relevant content of phenols and flavonoids, and we suggest the presence of chlorogenic acid, gallic acid, quercetin and theobromine. Acute administration of C. xanthocarpa aqueous extract has a dose-dependent hypotensive effect in normotensive rats, suggesting that the mechanism of action may be mediated by the renin-angiotensin system through AT1 receptor blockade (AT1R) and autonomic sympathetic response. Docking studies showed models that indicated an interaction between chlorogenic acid and quercetin with the active site of the AT1R. The findings of these coupling studies suggest the potential of the C. xanthocarpa constituents for use as preventive agents for blood pressure. In the treatment of rats with metabolic syndrome the extract increased the myosin ATPase activity and prevented reexpression of fetal MHC isoform, helping to prevent cardiac damage.