AUTHOR=Auth Pablo Alvarez , da Silva Gustavo Ratti , Amaral Eduarda Carolina , Bortoli Victor Fajardo , Manzano Mariana Inocencio , de Souza Lauro Mera , Lovato Evellyn Claudia Wietzikoski , Ribeiro-Paes João Tadeu , Gasparotto Junior Arquimedes , Lívero Francislaine Aparecida dos Reis 

TITLE=Croton urucurana Baill. Ameliorates Metabolic Associated Fatty Liver Disease in Rats

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.886122

DOI=10.3389/fphar.2022.886122

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Metabolic associated fatty liver disease (MAFLD) affects a quarter of the worldwide population, but no drug therapies have yet been developed. <italic>Croton urucurana</italic> Baill. (Euphorbiaceae) is a medicinal species, that is, widely distributed in Brazil. It is used in popular medicine to treat gastrointestinal, cardiovascular, and endocrine system diseases. However, its hepatoprotective and lipid-lowering effects have not yet been scientifically investigated.</p><p><bold>Aim of the study:</bold> The present study investigated the effects of an extract of <italic>C. urucurana</italic> in a rat model of MAFLD that was associated with multiple risk factors, including hypertension, smoking, and dyslipidemia.</p><p><bold>Material and Methods:</bold> The phytochemical composition of <italic>C. urucurana</italic> was evaluated by liquid chromatography-mass spectrometry. Spontaneously hypertensive 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 [C-] group), <italic>C. urucurana</italic> extract (30, 100, and 300 mg/kg), or simvastatin + enalapril (two standard reference drugs that are commonly used to treat dyslipidemia and hypertension, respectively). One group of rats that were not exposed to these risk factors was also evaluated (basal group). Blood was collected for the analysis of cholesterol, triglyceride, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. The liver and feces were collected for lipid quantification. The liver was also processed for antioxidant and histopathological analysis.</p><p><bold>Results:</bold> The main constituents of the <italic>C. urucurana</italic> extract were flavonoids, glycosides, and alkaloids. The model successfully induced MAFLD, reflected by increases in AST and ALT levels, and induced oxidative stress in the C- group. Treatment with the <italic>C. urucurana</italic> extract (300 mg/kg) and simvastatin + enalapril decreased plasma and hepatic lipid levels. In contrast to simvastatin + enalapril treatment, <italic>C. urucurana</italic> reduced AST and ALT levels. Massive lesions were observed in the liver in the C- group, which were reversed by treatment with the <italic>C. urucurana</italic> extract (300 mg/kg).</p><p><bold>Conclusion:</bold><italic>C. urucurana</italic> extract exerted promising hepatoprotective and lipid-lowering effects in a preclinical rat model of MAFLD.</p>