Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway
Copyright © 2020 Zhao, Zhang, Hu, Wang, Lu, Wu, Chen, Jin, Ji, Cao and Jiang..
Acetaminophen (APAP) overdose is the main cause of acute liver failure. Apigenin (API) is a natural dietary flavonol with high antioxidant capacity. Herein, we investigated protection by API against APAP-induced liver injury in mice, and explored the potential mechanism. Cell viability assays and mice were used to evaluate the effects of API against APAP-induced liver injury. Western blotting, immunofluorescence staining, RT-PCR, and Transmission Electron Microscope were carried out to determine the signalling pathways affected by API. Analysis of mouse serum levels of alanine/aspartate aminotransferase (ALT/AST), malondialdehyde (MDA), liver myeloperoxidase (MPO) activity, glutathione (GSH), and reactive oxygen species (ROS) revealed that API (80 mg/kg) owned protective effect on APAP-induced liver injury. Meanwhile, API ameliorated the decreased cell viability in L-02 cells incubated by APAP with a dose dependent. Furthermore, API promoted SIRT1 expression and deacetylated p53. Western blotting showed that API promoted APAP-induced autophagy, activated the NRF2 pathway, and inhibited the transcriptional activation of nuclear p65 in the presence of APAP. Furthermore, SIRT1 inhibitor EX-527 reduced protection by API against APAP-induced hepatotoxicity. Molecular docking results indicate potential interaction between API and SIRT1. API prevents APAP-induced liver injury by regulating the SIRT1-p53 axis, thereby promoting APAP-induced autophagy and ameliorating APAP-induced inflammatory responses and oxidative stress injury.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Frontiers in pharmacology - 11(2020) vom: 08., Seite 514 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Licong [VerfasserIn] |
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| Links: |
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| Themen: |
Acetaminophen-induced liver injury |
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| Anmerkungen: |
Date Revised 28.09.2020 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fphar.2020.00514 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310083109 |
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| 520 | |a Copyright © 2020 Zhao, Zhang, Hu, Wang, Lu, Wu, Chen, Jin, Ji, Cao and Jiang. | ||
| 520 | |a Acetaminophen (APAP) overdose is the main cause of acute liver failure. Apigenin (API) is a natural dietary flavonol with high antioxidant capacity. Herein, we investigated protection by API against APAP-induced liver injury in mice, and explored the potential mechanism. Cell viability assays and mice were used to evaluate the effects of API against APAP-induced liver injury. Western blotting, immunofluorescence staining, RT-PCR, and Transmission Electron Microscope were carried out to determine the signalling pathways affected by API. Analysis of mouse serum levels of alanine/aspartate aminotransferase (ALT/AST), malondialdehyde (MDA), liver myeloperoxidase (MPO) activity, glutathione (GSH), and reactive oxygen species (ROS) revealed that API (80 mg/kg) owned protective effect on APAP-induced liver injury. Meanwhile, API ameliorated the decreased cell viability in L-02 cells incubated by APAP with a dose dependent. Furthermore, API promoted SIRT1 expression and deacetylated p53. Western blotting showed that API promoted APAP-induced autophagy, activated the NRF2 pathway, and inhibited the transcriptional activation of nuclear p65 in the presence of APAP. Furthermore, SIRT1 inhibitor EX-527 reduced protection by API against APAP-induced hepatotoxicity. Molecular docking results indicate potential interaction between API and SIRT1. API prevents APAP-induced liver injury by regulating the SIRT1-p53 axis, thereby promoting APAP-induced autophagy and ameliorating APAP-induced inflammatory responses and oxidative stress injury | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a SIRT1 pathway | |
| 650 | 4 | |a SIRT1-p53 axis | |
| 650 | 4 | |a acetaminophen-induced liver injury | |
| 650 | 4 | |a antioxidant | |
| 650 | 4 | |a apigenin | |
| 650 | 4 | |a flavonol | |
| 650 | 4 | |a inflammatory response | |
| 650 | 4 | |a oxidative stress | |
| 700 | 1 | |a Zhang, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Chenqu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Long |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Mingming |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Guang |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yuanye |e verfasserin |4 aut | |
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