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Functional Teas from Penthorum chinense Pursh Alleviates Ethanol-Induced Hepatic Oxidative Stress and Autophagy Impairment in Zebrafish via Modulating the AMPK/p62/Nrf2/mTOR Signaling Axis

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Abstract

Penthorum chinense Pursh (PCP), a medicinal and edible plant, is widely used in many clinical liver diseases. Oxidative stress and autophagy impairment play crucial roles in the pathophysiology of alcoholic liver disease (ALD). Therefore, the aim of this study was to elucidate the mechanism of PCP in attenuating ethanol-induced liver injury. The liver-specific transgenic zebrafish larvae (lfabp: EGFP) at three days post-fertilization (3 dpf) were treated with different concentrations of PCP (100, 50 and 25 μg/mL) for 48 h, after soaked in a 350 mM ethanol for 32 h. Whole-mount oil red O, H&E staining and biochemical kits were used to detect fatty liver function and fat accumulation, western blot (WB) and immunofluorescence were used to determine proteins expression, and RT-qPCR was used to further verify the related gene expression. PCP restored zebrafish liver function. Additionally, PCP (as dose-dependent) blocked the expression of cytochrome P450 2E1 (CYP2E1), the production of intracellular reactive oxygen species (ROS) and alleviated liver fat accumulation and oxidative damage. PCP exerted its hepatoprotective function by downregulating the expression of kelch-like ECH-associated protein 1 (Keap1), up-regulating the expression of nucleus factor-E2-related factor 2 (Nrf2) (transferring to the nucleus), and attenuating systemic oxidative stress. Furthermore, PCP reduced the expression of sequestosome 1 (p62/SQSTM1, p62), Atg13, and Beclin 1, up-regulating autophagy signaling pathway. Taken together, the molecular evidence that PCP protected the ethanol-induced hepatic oxidative stress and autophagy impairment through activating AMPK/p62/Nrf2/mTOR signaling axis.

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Abbreviations

ACC1:

Acetyl-CoA carboxylase 1

ADH:

Alcohol dehydrogenase

ALD:

Alcoholic liver disease

ALT:

Alanine transaminase

AMPK:

Activated protein kinase

AST:

Aspartate aminotransferase

CAT:

Catalase

DCF-DA:

2′,7′-Dichlorodihydrofluorescein diacetate

CYP450:

Cytochrome P450

ER:

Endoplasmic reticulum

IOD:

Integral optical density

GSH:

Glutathione

Keap1:

Kelch-like ECH-associated protein 1

Lfabp: EGFP:

Liver-specific transgenic zebrafish larvae

FAS:

Fatty acid synthetase

MDA:

Malondialdehyde

MEOS:

Microsomal ethanol oxidation system

Nrf2:

Nucleus factor-E2-related factor 2

PCP:

Penthorum chinense Pursh

ROS:

Reactive oxygen species

RT-qPCR:

Quantitative reverse transcriptase-polymerase chain reaction

p62/SQSTM1:

Sequestosome 1

SOD:

Superoxide dismutase

SREBP-1C:

Sterol regulatory component binding protein 1C

TC:

Total cholesterol

TG:

Triglyceride

H&E:

Hematoxylin and eosin

HPLC:

High performance liquid chromatography

WHO:

World Health Organization

3 dpf:

Three days post-fertilization

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Authors and Affiliations

  1. State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu, 611137, China

    Xingtao Zhao, Mengting Zhou, Ying Deng, Chaocheng Guo, Li Liao, Linfeng He, Cheng Peng & Yunxia Li

  2. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Sichuan Province, 1166 Liutai Avenue, Wenjiang District, Chengdu, 611137, China

    Xingtao Zhao, Mengting Zhou, Ying Deng, Chaocheng Guo, Li Liao, Linfeng He, Cheng Peng & Yunxia Li

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Correspondence to Yunxia Li.

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All data generated or analyzed during this study are included in this article and its supplementary materials files and all authors declare that there are no conflicts of interests and consent to submit.

Innovation Team and Talent Cultivation Program of National Administration of Traditional Chinese Medicine (Grant No. ZYYCXTD-D-202209), National Science Foundation of China (Grant No. 8189101, 81891012, 8163010, U19A2010), Sichuan Science and Technology Program (Grant No. 2021JDRC0041), Sichuan TCM Science and Technology Industry Innovation Team (NO. 2022C001).

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The Institutional Animal and Use Committee of Chengdu University of Traditional Chinese Medicine (No. SYXK (CHUAN) 2014–128).

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Zhao, X., Zhou, M., Deng, Y. et al. Functional Teas from Penthorum chinense Pursh Alleviates Ethanol-Induced Hepatic Oxidative Stress and Autophagy Impairment in Zebrafish via Modulating the AMPK/p62/Nrf2/mTOR Signaling Axis. Plant Foods Hum Nutr 77, 514–520 (2022). https://doi.org/10.1007/s11130-022-01010-0

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