Campomanesia xanthocarpa, chemical composition, hypertension, cardiovascular system, AT1 receptor, chlorogenic acid, quercetin, myosin

As doencas cardiovasculares sao a principal causa de morte no Brasil e estao fortemente associadas a disturbios metabolicos como a sindrome metabolica. A sindrome metabolica e caracterizada pela cocorrencia de fatores de risco cardiovasculares como hipertensao, hiperinsulinemia, a glicose, obesidade central e dislipidemia. Campomanesia xanthocarpa, conhecida no Brasil como Guabiroba, tem sido utilizada empiricamente devido ao seu potencial efeito na reducao dos niveis de colesterol sanguineos, e para varias condicoes, incluindo doencas inflamatorias, renais, digestivas, dislipidemias e outras. O objetivo deste estudo foi analisar a composicao quimica e investigar os efeitos do extrato aquoso de C. xanthocarpa na pressao arterial de ratos normotensos agudamente, bem como seu possivel mecanismo de acao, in vivo e in silico. Alem disso, tambem se avaliou os efeitos do extrato aquoso de C. xanthocarpa sobre a atividade da ATPase miosinica e expressao genica de marcadores cardiacos em ratos com sindrome metabolica induzida por uma dieta rica em frutose. O extrato foi analisado quanto aos compostos fenolicos totais e ao teor total de flavonoides. Os componentes quimicos foram determinados por analise de HPLC. Para a avaliacao aguda, a pressao arterial sistolica e diastolica e a frequencia cardiaca foram medidas na presenca de extrato e com administracao de farmacos. Para avaliacao dos animais com sindrome metabolica, os animais foram tratados durante 30 dias com extrato aquoso das folhas preparado por infusao. A extracao de miosina cardiaca foi realizada com centrifugacao de alta forca ionica, a medida da atividade da ATPase miosinica foi quantificada pelo fosfato inorganico liberado atraves de metodo colorimetrico e expresso em nmolPi/min/mg de proteina. A expressao genica de α-MHC, β-MHC, fator natriuretico atrial e α-actina esqueletica foi avaliada por PCR em tempo real. As folhas de C. xanthocarpa apresentaram conteudo relevante de fenois e flavonoides, e sugerimos a presenca de acido clorogenico, acido galico, quercetina e teobromina. A administracao aguda de extrato aquoso de C. xanthocarpa tem um efeito hipotensor dose-dependente em ratos normotensos, sugerindo que o mecanismo de acao pode ser mediado pelo sistema renina-angiotensina atraves do bloqueio do receptor AT1 (AT1R) e resposta simpatica autonomica. Estudos “docking” mostraram modelos que indicaram uma interacao entre acido clorogenico e quercetina com o sitio de ligacao do AT1R. Os achados desses estudos de acoplamento sugerem o potencial dos constituintes de C. xanthocarpa para uso como agentes preventivos para a pressao sanguinea. No tratamento de ratos com sindrome metabolica o extrato aumentou a atividade de ATPase miosinica e impediu a reexpressao da isoforma fetal da MHC, auxiliando na prevencao do dano cardiaco. 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.