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

Abstract

Background: Metabolic associated fatty liver disease (MAFLD) affects a quarter of the worldwide population, but no drug therapies have yet been developed. Croton urucurana 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.Aim of the study: The present study investigated the effects of an extract of C. urucurana in a rat model of MAFLD that was associated with multiple risk factors, including hypertension, smoking, and dyslipidemia.Material and Methods: The phytochemical composition of C. urucurana 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), C. urucurana 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.Results: The main constituents of the C. urucurana 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 C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased plasma and hepatic lipid levels. In contrast to simvastatin + enalapril treatment, C. urucurana reduced AST and ALT levels. Massive lesions were observed in the liver in the C- group, which were reversed by treatment with the C. urucurana extract (300 mg/kg).Conclusion:C. urucurana extract exerted promising hepatoprotective and lipid-lowering effects in a preclinical rat model of MAFLD.

Bridging the Gap: Exploring the Preclinical Potential of Pereskia grandifolia in Metabolic‐Associated Fatty Liver Disease

“…Te reduction of these markers of oxidative stress following administration of the plant extract suggests its ability to neutralize free radicals and protect liver cells against oxidative damage. Preclinical studies involving multifactorial risk-induced liver disease previously conducted support the results of this research and have highlighted the importance of the antioxidant efect of medicinal plants as a fundamental component in the construction of therapeutic efect [12][13][14].…”

“…In the study conducted by Auth et al [14], spontaneously hypertensive rats were exposed to a high-cholesterol diet and cigarette smoke for a period of 10 weeks. In the fnal 5 weeks of this period, the rats were subjected to various treatments including diferent doses of Croton urucurana extract, simvastatin + enalapril, or a vehicle (serving as the negative control).…”

“…Animals were randomly divided into experimental groups, with 8 rats per group. Te selection of this group size was based on previous results from similar experimental protocols and adhered to the 3R principles (reduce, refne, and replace) [12][13][14][27][28][29]. Weights were assessed on a weekly basis using an analytical balance.…”

“…In this line, animal models with multiple risk factors associated with MAFLD can provide valuable information on the complex pathogenesis of the disease and potential therapeutic targets. Te proposition of these animal models is justifed by the need to address the complex nature of MAFLD and the limited efectiveness of current treatments [12][13][14][15]. By utilizing these models, it is possible to enhance the likelihood of identifying promising therapeutic candidates for further development and clinical trials [16].…”