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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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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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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DOI: https://doi.org/10.1007/s11130-022-01010-0