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甘草素通过 AMPK/SIRT1/NF-κB 信号通路抑制 H 2 O 2 诱导的 H9c2 细胞氧化应激损伤。

Liquiritin inhibits H O -induced oxidative stress injury in H9c2 cells via the AMPK/SIRT1/NF-κB signaling pathway.

机构信息

Graduate School of Anhui University of Chinese Medicine, Hefei, China.

Department of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.

出版信息

J Food Biochem. 2022 Oct;46(10):e14351. doi: 10.1111/jfbc.14351. Epub 2022 Aug 5.

DOI:10.1111/jfbc.14351
PMID:35929638
Abstract

Heart failure (HF) is a serious disease with high mortality. Oxidative stress plays a vital role in its occurrence and development. Licorice is commonly used to treat HF in traditional Chinese medicine. Liquiritin, the main ingredient of licorice, has antioxidant and anti-inflammatory properties, but the mechanism against oxidative stress in cardiomyocytes has not been reported. Establishment of oxidative damage model in H9c2 cells by hydrogen peroxide (H O ). Liquiritin (5, 10, 20 μmol/L) could significantly prevent the loss of cell viability and decrease the apoptosis rate. It can reduce the levels of reactive oxygen species (ROS), malonedialdehyde (MDA), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and increase the activity of ATP, superoxidedismutase (SOD), glutathione peroxide (GSH-px), glutathione reductase (GR) and catalase (CAT) to alleviate oxidative stress and inflammation in a dose-dependent manner. Liquiritin was found to be related to AMP-Activated Protein Kinase (AMPK) pathway by molecular docking. Western blotting (WB) and quantitative reverse transcription PCR (RT-qPCR) confirmed that liquiritin could promote AMPKα phosphorylation and sirtuin 1 (SIRT1) protein expression, and inhibit phosphorylation of nuclear factor kappa B p65 (NF-κB p65). Compound C, EX 527, and PDTC can reverse the effects of liquiritin, indicating that its antioxidant effect is achieved by regulating AMPK/SIRT1/NF-κB signaling pathway. PRACTICAL APPLICATIONS: Heart failure is one of the most common cardiovascular diseases, and its treatment remains a worldwide problem. Licorice is a food and dietary supplement that has been used widely in traditional Chinese medicine (TCM). Liquiritin is one of the main active components of licorice, which has antioxidant and anti-inflammatory pharmacological effects. This study revealed the mechanism of licorice against oxidative damage of H9c2 cardiomyocytes, and provided a scientific basis for liquiritin as an antioxidant in the treatment of heart failure.

摘要

心力衰竭(HF)是一种死亡率很高的严重疾病。氧化应激在其发生和发展中起着至关重要的作用。甘草在中医中常被用来治疗 HF。甘草的主要成分甘草素具有抗氧化和抗炎特性,但尚未报道其在心肌细胞对抗氧化应激的机制。通过过氧化氢(H 2 O 2 )建立 H9c2 细胞氧化损伤模型。甘草素(5、10、20 μmol/L)可显著防止细胞活力丧失和凋亡率降低。它可以降低活性氧(ROS)、丙二醛(MDA)、乳酸脱氢酶(LDH)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)的水平,并增加 ATP、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-px)、谷胱甘肽还原酶(GR)和过氧化氢酶(CAT)的活性,从而减轻氧化应激和炎症,呈剂量依赖性。通过分子对接发现甘草素与 AMP 激活的蛋白激酶(AMPK)途径有关。Western blot(WB)和定量逆转录 PCR(RT-qPCR)证实,甘草素可以促进 AMPKα 磷酸化和 SIRT1 蛋白表达,并抑制核因子 kappa B p65(NF-κB p65)磷酸化。化合物 C、EX 527 和 PDTC 可以逆转甘草素的作用,表明其抗氧化作用是通过调节 AMPK/SIRT1/NF-κB 信号通路实现的。实际应用:心力衰竭是最常见的心血管疾病之一,其治疗仍是全球性问题。甘草是一种食品和膳食补充剂,在中医中广泛使用。甘草素是甘草的主要活性成分之一,具有抗氧化和抗炎的药理作用。本研究揭示了甘草素对抗 H9c2 心肌细胞氧化损伤的机制,为甘草素作为治疗心力衰竭的抗氧化剂提供了科学依据。

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