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高脂高果糖饮食诱导的非酒精性脂肪肝病小鼠模型中通过脂生成和脂肪酸氧化的平衡缓解非酒精性脂肪肝病。

Alleviates Non-Alcoholic Fatty Liver by Balancing Lipogenesis and Fatty Acid Oxidation in a High-Fat, High-Fructose Diet Mice Model.

机构信息

Institute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, Korea.

Liver and Immunology Research Center, Daejeon Korean Medicine Hospital, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, Korea.

出版信息

Cells. 2021 Dec 22;11(1):23. doi: 10.3390/cells11010023.

Abstract

, a medicinal herb, is traditionally used as an antidote, diuretic, and antipyretic in eastern Asia. The current study aimed to investigate the anti-fatty liver capacity of the ethanol extract of (CAE) using a 10-week high-fat, high-fructose diet mouse model. A six-week treatment of CAE (from the fifth week) significantly attenuated the weights of the body, liver, and mesenteric fat without a change in diet intake. CAE also considerably restored the alterations of serum aminotransferases and free fatty acid, fasting blood glucose, serum and hepatic triglyceride, and total cholesterol, as well as platelet and leukocyte counts. Meanwhile, CAE ameliorated hepatic injury and lipid accumulation, as evidenced by histopathological and immunofluorescence observations. Additionally, CAE significantly lowered the elevation of hepatic TNF-α, the TNF-α/IL-10 ratio, fecal endotoxins, and the abundance of Gram-negative bacteria. Hepatic lipogenesis and β-oxidation-related proteins and gene expression, including PPAR-α, SREBP-1, SIRT1, FAS, CTP1, etc., were normalized markedly by CAE. In particular, the AMPK, a central regulator of energy metabolism, was phosphorylated by CAE at an even higher rate than metformin. Overall, CAE exerts anti-hepatic steatosis effects by reducing lipogenesis and enhancing fatty acid oxidation. Consequently, is expected to be a promising candidate for treating chronic metabolic diseases.

摘要

,一种药用草本植物,在东亚传统上被用作解毒剂、利尿剂和解热剂。本研究旨在通过 10 周高脂肪、高果糖饮食的小鼠模型来研究 的抗脂肪肝能力。从第五周开始的六周 治疗(CAE)显著减轻了体重、肝脏和肠系膜脂肪的重量,而饮食摄入量没有变化。CAE 还显著恢复了血清转氨酶和游离脂肪酸、空腹血糖、血清和肝甘油三酯和总胆固醇以及血小板和白细胞计数的改变。同时,CAE 通过组织病理学和免疫荧光观察改善了肝损伤和脂质堆积。此外,CAE 显著降低了肝 TNF-α、TNF-α/IL-10 比值、粪便内毒素和革兰氏阴性菌丰度的升高。CAE 显著调节了肝脂肪生成和β氧化相关蛋白和基因的表达,包括 PPAR-α、SREBP-1、SIRT1、FAS、CTP1 等。特别是,CAE 以比二甲双胍更高的速度磷酸化 AMPK,这是能量代谢的核心调节剂。总的来说,CAE 通过减少脂肪生成和增强脂肪酸氧化来发挥抗肝脂肪变性作用。因此,有望成为治疗慢性代谢性疾病的有前途的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f743/8750091/9f0ce95ac8e4/cells-11-00023-g001.jpg

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