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贝利。改善大鼠代谢相关脂肪性肝病。

Baill. Ameliorates Metabolic Associated Fatty Liver Disease in Rats.

作者信息

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

机构信息

Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama, Brazil.

Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Paranaense University, Umuarama, Brazil.

出版信息

Front Pharmacol. 2022 May 20;13:886122. doi: 10.3389/fphar.2022.886122. eCollection 2022.

Abstract

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

摘要

代谢相关脂肪性肝病(MAFLD)影响着全球四分之一的人口,但尚未开发出药物疗法。Baill.(大戟科)是一种药用植物,广泛分布于巴西。它在民间医学中用于治疗胃肠道、心血管和内分泌系统疾病。然而,其肝脏保护和降脂作用尚未得到科学研究。本研究在与多种风险因素相关的MAFLD大鼠模型中,包括高血压、吸烟和血脂异常,研究了Baill.提取物的作用。通过液相色谱 - 质谱法评估了Baill.的植物化学成分。自发性高血压大鼠接受富含0.5%胆固醇的饮食,并暴露于香烟烟雾中(每天9支香烟,持续10周)。在最后5周,动物经口给予载体(阴性对照组[C - ])、Baill.提取物(30、100和300mg/kg)或辛伐他汀+依那普利(两种分别常用于治疗血脂异常和高血压的标准参考药物)。还评估了一组未暴露于这些风险因素的大鼠(基础组)。采集血液分析胆固醇、甘油三酯、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平。收集肝脏和粪便进行脂质定量。肝脏也进行抗氧化和组织病理学分析。Baill.提取物的主要成分是黄酮类、糖苷和生物碱。该模型成功诱导了MAFLD,表现为AST和ALT水平升高,并在C - 组中诱导了氧化应激。用Baill.提取物(300mg/kg)和辛伐他汀+依那普利治疗可降低血浆和肝脏脂质水平。与辛伐他汀+依那普利治疗相反,Baill.降低了AST和ALT水平。在C - 组肝脏中观察到大量病变,用Baill.提取物(300mg/kg)治疗可使其逆转。Baill.提取物在MAFLD的临床前大鼠模型中发挥了有前景的肝脏保护和降脂作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6ef/9164250/f0e7269e7f32/fphar-13-886122-g001.jpg

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