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

Priscila Megda João Job Zago; Gustavo Ratti da Silva; Eduarda Carolina Amaral; Lorena Neris Barboza; Fernanda de Abreu Braga; Bethânia Rosa Lorençone; Aline Aparecida Macedo Marques; Karyne Garcia Tafarelo Moreno; Patrícia Regina Terço Leite; Alan de Almeida Veiga; Lauro Mera de Souza; Roosevelt Isaias Carvalho Souza; Ariany Carvalho Dos Santos; João Tadeu Ribeiro-Paes; Arquimedes Gasparotto Junior; Francislaine Aparecida Dos Reis Lívero

doi:10.1155/2021/6580458

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

Evid Based Complement Alternat Med. 2021 Nov 15:2021:6580458. doi: 10.1155/2021/6580458. eCollection 2021.

Authors

Priscila Megda João Job Zago¹, Gustavo Ratti da Silva², Eduarda Carolina Amaral¹, Lorena Neris Barboza¹, Fernanda de Abreu Braga¹, Bethânia Rosa Lorençone³, Aline Aparecida Macedo Marques³, Karyne Garcia Tafarelo Moreno³, Patrícia Regina Terço Leite³, Alan de Almeida Veiga⁴, Lauro Mera de Souza⁴, Roosevelt Isaias Carvalho Souza⁵, Ariany Carvalho Dos Santos⁵, João Tadeu Ribeiro-Paes⁶, Arquimedes Gasparotto Junior³, Francislaine Aparecida Dos Reis Lívero⁷

Affiliations

¹ Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Paranaense University, Umuarama, Paraná, Brazil.
² Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama, Paraná, Brazil.
³ Laboratory of Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul, Brazil.
⁴ Institute of Research Pelé Pequeno Príncipe, Pequeno Príncipe Faculty, Curitiba, Paraná, Brazil.
⁵ Laboratory of Histology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul, Brazil.
⁶ Laboratory of Genetics and Cell Therapy, São Paulo State University, Assis, São Paulo, Brazil.
⁷ Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Post-Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama, Paraná, Brazil.

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.