Multiple Risk Factors for Heart Disease: A Challenge to the Ethnopharmacological Use of Croton urucurana Baill

Abstract

Croton urucurana Baill. is a native Brazilian tree, popularly known as "sangra-d'água" or "sangue-de-dragão," based on the red resinous sap of the trunk. Its use has been transmitted through generations based on popular tradition that attributes analgesic, anti-inflammatory, and cardioprotective properties to the tree. However, its cardioprotective effects have not yet been scientifically investigated. Thus, the present study investigated the pharmacological response to an ethanol-soluble fraction from the leaves of C. urucurana in Wistar rats exposed to smoking and dyslipidemia, two important cardiovascular risk factors. The extract was evaluated by high-performance liquid chromatography. Wistar rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day for 10 weeks). During the last 5 weeks, the animals were orally treated with vehicle (negative control group), C. urucurana extract (30, 100, and 300 mg/kg), or simvastatin (2.5 mg/kg) + enalapril (15 mg/kg). One group of rats that was not exposed to these risk factors was also evaluated (basal group). Electrocardiograms and systolic, diastolic, and mean blood pressure were measured. Blood was collected to measure total cholesterol, triglycerides, urea, and creatinine. The heart and kidneys were collected and processed for oxidative status and histopathological evaluation. The phytochemical analysis revealed different classes of flavonoids and condensed tannins. The model induced dyslipidemia and cardiac and renal oxidative stress and increased levels of urea and creatinine in the negative control group. Treatment with the C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased cholesterol and triglyceride levels. In contrast to simvastatin + enalapril treatment, the C. urucurana extract exerted cardiac and renal antioxidant effects. No alterations of electrocardiograms, blood pressure, or histopathology were observed between groups. These findings indicate that C. urucurana exerts lipid-lowering, renal, and cardioprotective effects against oxidative stress in a preclinical model of multiple risk factors for heart disease.

Figure 1

HPLC analysis of the ethanol-soluble fraction of the leaf extract of C. urucurana (A) and authentic standards (B). GA: gallic acid; cat: catechin; FA: ferulic acid; VA: vanillic acid; SA: syringic acid; rut: rutin; Isoq: isoquercitrin; Hyp: hyperoside; Myr: myricetin; Quer: quercetin; Kaemp: kaempferol.

Figure 2

Effects of Croton urucurana on biochemical profile. Plasma levels of (a) cholesterol (mg/dl), (b) triglycerides (mg/dl), (c) urea (mg/dl), and (d) creatinine (mg/dl) in nondyslipidemic and nonsmoking rats (basal group) and dyslipidemic and smoking rats that were treated with vehicle (negative control (C−)), Croton urucurana extract (30, 100, and 300 mg/kg), or simvastatin + enalapril (SIM + ENAL). The data are expressed as mean ± SEM. ^ap < 0.05 versus basal group; ^bp < 0.05 versus C− group (one-way ANOVA followed by Newman–Keuls post hoc test).

Figure 3

Antioxidant effects of Croton urucurana extract. Cardiac levels of (a) reduced glutathione, (b) lipoperoxidation, and (c) superoxide dismutase and renal levels of (d) reduced glutathione, (e) lipoperoxidation, and (f) superoxide dismutase in nondyslipidemic and nonsmoking Wistar rats (basal group) and dyslipidemic and smoking rats that were treated with vehicle (negative control (C−)), Croton urucurana extract (30, 100, and 300 mg/kg), or simvastatin + enalapril (SIM + ENAL). The data are expressed as mean ± SEM. ^ap < 0.05 versus basal group; ^bp < 0.05 versus C− group (one-way ANOVA followed by Newman–Keuls post hoc test).

Figure 4

Cardiac and renal histopathological analysis. Hematoxylin/eosin staining of the heart and kidney from nondyslipidemic and nonsmoking rats (basal group) and dyslipidemic and smoking rats that were treated with vehicle (negative control (C−)), 300 mg/kg Croton urucurana extract (croton 300), and simvastatin + enalapril (SIM + ENAL). 40 × magnification.