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天然化合物抗非酒精性脂肪性肝病:LKB1/AMPK信号通路参与情况的综述

Natural compounds against nonalcoholic fatty liver disease: A review on the involvement of the LKB1/AMPK signaling pathway.

作者信息

Omidkhoda Navid, Mahdiani Sina, Hayes A Wallace, Karimi Gholamreza

机构信息

Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Phytother Res. 2023 Dec;37(12):5769-5786. doi: 10.1002/ptr.8020. Epub 2023 Sep 25.

Abstract

Although various therapeutic approaches are used to manage nonalcoholic fatty liver disease (NAFLD), the best approach to NAFLD management is unclear. NAFLD is a liver disorder associated with obesity, metabolic syndrome, and diabetes mellitus. NAFLD progression can lead to cirrhosis and end-stage liver disease. Hepatic kinase B1 (LKB1) is an upstream kinase of 5'-adenosine monophosphate-activated protein kinase (AMPK), a crucial regulator in hepatic lipid metabolism. Activation of LKB1/AMPK inhibits fatty acid synthesis, increases mitochondrial β-oxidation, decreases the expression of genes encoding lipogenic enzymes, improves nonalcoholic steatohepatitis, and suppresses NAFLD progression. One potential opening for new and safe chemicals that can tackle the NAFLD pathogenesis through the LKB1-AMPK pathway includes natural bioactive compounds. Accordingly, we summarized in vitro and in vivo studies regarding the effect of natural bioactive compounds such as a few members of the polyphenols, terpenoids, alkaloids, and some natural extracts on NAFLD through the LKB1/AMPK signaling pathway. This manuscript may shed light on the way to finding a new therapeutic agent for NAFLD management.

摘要

尽管采用了各种治疗方法来管理非酒精性脂肪性肝病(NAFLD),但NAFLD管理的最佳方法尚不清楚。NAFLD是一种与肥胖、代谢综合征和糖尿病相关的肝脏疾病。NAFLD的进展可导致肝硬化和终末期肝病。肝激酶B1(LKB1)是5'-腺苷单磷酸激活蛋白激酶(AMPK)的上游激酶,AMPK是肝脏脂质代谢的关键调节因子。LKB1/AMPK的激活抑制脂肪酸合成,增加线粒体β-氧化,降低编码脂肪生成酶的基因表达,改善非酒精性脂肪性肝炎,并抑制NAFLD进展。通过LKB1-AMPK途径解决NAFLD发病机制的新的安全化学品的一个潜在突破口包括天然生物活性化合物。因此,我们总结了体外和体内研究,这些研究涉及多酚、萜类、生物碱的一些成员以及一些天然提取物等天然生物活性化合物通过LKB1/AMPK信号通路对NAFLD的影响。本手稿可能为寻找用于NAFLD管理的新治疗剂指明方向。

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