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山楂通过激活 AMPK 诱导的 SREBP1 抑制和激活 PPARα 来预防高脂肪饮食诱导的大鼠肝脂肪变性。

Crataegus aronia prevents high-fat diet-induced hepatic steatosis in rats by activating AMPK-induced suppression of SREBP1 and activation of PPARα.

机构信息

Department of Medicine, Cardiology Section, College of Medicine, King Khalid University (KKU), Abha, Saudi Arabia.

Department of Internal Medicine, College of Medicine, King Khalid University (KKU), Abha, Saudi Arabia.

出版信息

J Food Biochem. 2021 Nov;45(11):e13945. doi: 10.1111/jfbc.13945. Epub 2021 Sep 29.

DOI:10.1111/jfbc.13945
PMID:34585409
Abstract

This study examined if the aqueous extract of Crataegus aronia (C. aronia) can prevent high-fat diet (HFD)-induced hepatic steatosis in rats by activating AMPK. Adult male Wistar rats were fed either a control diet or HFD for 12 weeks and treated either with vehicle (normal saline) or C. aronia extract (200 mg/kg/orally), daily. Also, hepatocytes were treated with increasing concentrations of the extract in the presence or absence of compound C (CC), an AMPK inhibitor. C. aronia prevented the increase in serum and hepatic lipids, reduced hepatic levels of reactive oxygen species, and increased hepatic glutathione and superoxide dismutase levels. It also downregulated the hepatic expression of SREBP1/2, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase but stimulated the activity of AMPK and levels of peroxisome proliferator-activated receptor-alpha. Similar effects were reported in the cultured cells, in a dose-dependent manner but were prevented by CC. In conclusion, C. aronia ameliorates HFD-induced hepatic steatosis and oxidative stress by activating AMPK. PRACTICAL APPLICATIONS: The use of the aqueous extract of Crataegus aronia has been extensively used during the last years in traditional medicine to treat chronic disorders including nonalcoholic fatty liver disease. The findings of this study support these findings and suggest that oral administration of C. aronia aqueous extract has potent hypoglycemic effect and demonstrate the mechanism of action mimics such drugs such as metformin and involves activation of AMPK and peroxisome proliferator-activated receptor-alpha. These findings are very encouraging for further biochemical analysis and isolation of active ingredients responsible for these effects to be used in more clinical trials.

摘要

本研究旨在探讨山茱萸(Crataegus aronia)水提物是否通过激活 AMPK 来预防高脂肪饮食(HFD)诱导的大鼠肝脂肪变性。成年雄性 Wistar 大鼠分别喂食对照饮食或 HFD 12 周,并分别给予载体(生理盐水)或 C. aronia 提取物(200mg/kg/口服),每天一次。此外,在存在或不存在 AMPK 抑制剂化合物 C(CC)的情况下,用递增浓度的提取物处理肝细胞。C. aronia 可防止血清和肝脂质增加,减少肝内活性氧水平,并增加肝内谷胱甘肽和超氧化物歧化酶水平。它还下调了 SREBP1/2、脂肪酸合酶和 3-羟-3-甲基戊二酰辅酶 A 还原酶的肝表达,但刺激了 AMPK 的活性和过氧化物酶体增殖物激活受体-α的水平。在培养的细胞中也报告了类似的作用,呈剂量依赖性,但被 CC 阻止。总之,C. aronia 通过激活 AMPK 改善 HFD 诱导的肝脂肪变性和氧化应激。

实际应用

山茱萸的水提取物在过去几年中被广泛用于传统医学中,用于治疗包括非酒精性脂肪性肝病在内的慢性疾病。本研究的结果支持这些发现,并表明 C. aronia 水提取物的口服给药具有很强的降血糖作用,并证明其作用机制类似于二甲双胍等药物,涉及激活 AMPK 和过氧化物酶体增殖物激活受体-α。这些发现非常令人鼓舞,可以进行进一步的生化分析和分离负责这些作用的活性成分,以用于更多的临床试验。

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