Quercetin mitigates ethanol-induced hepatic steatosis in zebrafish via P2X7R-mediated PI3K/ Keap1/Nrf2 signaling pathway

Zhao, Xingtao; Gong, Lihong; Wang, Cheng; Liu, Meichen; Hu, Naihua; Dai, Xuyang; Peng, Cheng; Li, Yunxia

doi:10.1016/j.jep.2020.113569

Cited by 49 publications

(29 citation statements)

References 45 publications

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“…For example, Ma et al demonstrated that inhibition of ASK1 and p38MAPK, which relay oxidative stress to cell death signaling, afforded protection against hepatocyte death induced by ethanol feeding in mice [ 88 ]. In addition, recent studies have demonstrated that the Nrf2/ARE pathway might be a useful target for reducing ethanol-induced oxidative stress and liver injury [ 20 , 89 , 90 , 91 , 92 , 93 , 94 ].…”

Section: Oxidative Stress-related Pathogenic Mechanisms Of Aldmentioning

confidence: 99%

Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

Yang

Cho

Hwang

2022

IJMS

113

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Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.

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Section: Oxidative Stress-related Pathogenic Mechanisms Of Aldmentioning

confidence: 99%

Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

Yang

Cho

Hwang

2022

IJMS

113

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“…It also had a similar hepatoprotective mechanism in zebrafish with respect to the alcoholic fatty liver model (X. Zhao et al, 2020).…”

Section: Pi3k/aktmentioning

confidence: 91%

“…Moreover, quercetin regulated the P2X7R‐mediated PI3K/Keap1/Nrf2 oxidative stress signaling pathway. It also had a similar hepatoprotective mechanism in zebrafish with respect to the alcoholic fatty liver model (X. Zhao et al, 2020).…”

Section: Antifatty Hepatitis Property Of Quercetinmentioning

confidence: 92%

“…Recently, it was reported that inhibition of P2X7R activation by quercetin also attenuated Keap 1/Nrf2 oxidative stress in alcoholic fatty liver in zebrafish (X. Zhao et al, 2020). Dihydroquercetin modulated adipogenesis and improved alcoholic hepatic steatosis by modulating P2X7R‐NLRP3‐inflammatory vesicle activation mediators in HepG2 cells (Y. Zhang et al, 2018), suggesting P2X7R is a new target and needs further study.…”

Section: Antifatty Hepatitis Property Of Quercetinmentioning

confidence: 99%

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Quercetin as a protective agent for liver diseases: A comprehensive descriptive review of the molecular mechanism

Zhao

Wang

Deng

et al. 2021

Phytotherapy Research

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Quercetin is the major representative of the flavonoid subgroup of flavones, with good pharmacological activities for the treatment of liver diseases, including liver steatosis, fatty hepatitis, liver fibrosis, and liver cancer. It can significantly influence the development of liver diseases via multiple targets and multiple pathways via antifat accumulation, anti‐inflammatory, and antioxidant activity, as well as the inhibition of cellular apoptosis and proliferation. Despite extensive research on understanding the mechanism of quercetin in the treatment of liver diseases, there are still no targeted therapies available. Thus, we have comprehensively searched and summarized the different targets of quercetin in different stages of liver diseases and concluded that quercetin inhibited inflammation of the liver mainly through NF‐κB/TLR/NLRP3, reduced PI3K/Nrf2‐mediated oxidative stress, mTOR activation in autophagy, and inhibited the expression of apoptotic factors associated with the development of liver diseases. In addition, quercetin showed different mechanisms of action at different stages of liver diseases, including the regulation of PPAR, UCP, and PLIN2‐related factors via brown fat activation in liver steatosis. The compound inhibited stromal ECM deposition at the liver fibrosis stage, affecting TGF1β, endoplasmic reticulum stress (ERs), and apoptosis. While at the final liver cancer stage, inhibiting cancer cell proliferation and spread via the hTERT, MEK1/ERK1/2, Notch, and Wnt/β‐catenin‐related signaling pathways. In conclusion, quercetin is an effective liver protectant. We hope to explore the pathogenesis of quercetin in different stages of liver diseases through the review, so as to provide more accurate targets and theoretical basis for further research of quercetin in the treatment of liver diseases.

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“…Zeng et al proved that quercetin activated AMPK and increased the colocalisation of hepatic LC3II and Perilipin 2 (PLIN2) to promote lipophagy, thereby improving the steatosis of mice with ALD ( Zeng H. et al, 2019 ). Zhao et al also confirmed that quercetin directly mitigates alcohol-induced hepatic steatosis in zebrafish via the regulation of the PI3K/Keap1/Nrf2 pathway ( Zhao et al, 2021 ).…”

Section: Natural Compounds and Their Mechanisms Action In The Treatment Of Alcoholic Liver Diseasementioning

confidence: 92%

Natural Compounds: A Potential Treatment for Alcoholic Liver Disease?

et al. 2021

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Excessive alcohol intake is a direct cause of alcoholic liver disease (ALD). ALD usually manifests as fatty liver in the initial stage and then develops into alcoholic hepatitis (ASH), fibrosis and cirrhosis. Severe alcoholism induces extensive hepatocyte death, liver failure, and even hepatocellular carcinoma (HCC). Currently, there are few effective clinical means to treat ALD, except for abstinence. Natural compounds are a class of compounds extracted from herbs with an explicit chemical structure. Several natural compounds, such as silymarin, quercetin, hesperidin, and berberine, have been shown to have curative effects on ALD without side effects. In this review, we pay particular attention to natural compounds and developing clinical drugs based on natural compounds for ALD, with the aim of providing a potential treatment for ALD.

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Quercetin mitigates ethanol-induced hepatic steatosis in zebrafish via P2X7R-mediated PI3K/ Keap1/Nrf2 signaling pathway

Cited by 49 publications

References 45 publications

Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

Quercetin as a protective agent for liver diseases: A comprehensive descriptive review of the molecular mechanism

Natural Compounds: A Potential Treatment for Alcoholic Liver Disease?

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