ReferenceID 3919
Nrf2-mediated liver protection by esculentoside A against acetaminophen toxicity through the AMPK/Akt/GSK3β pathway
Free Radic Biol Med
Acetaminophen (APAP) overdose accounts for the majority of acute liver failure cases, and oxidative stress plays a key role in its toxic effects. Esculentoside A (EsA) has anti-oxidant activities, but its therapeutic po
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Record Fields
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- Reference Id
- 3919
- Evidence Id
- 20509
- Core Evidence Id
- 20509
- Source Reference Id
- 1107
- Herb2 Reference Id
- HBREF001859
- Subject Paper Key
- HBIN025762_27836781
- Pubmed Id
- 27836781
- Doi
- 10.1016/j.freeradbiomed.2016.11.009
- Paper Title
- Nrf2-mediated liver protection by esculentoside A against acetaminophen toxicity through the AMPK/Akt/GSK3β pathway
- Paper Abstract
- Acetaminophen (APAP) overdose accounts for the majority of acute liver failure cases, and oxidative stress plays a key role in its toxic effects. Esculentoside A (EsA) has anti-oxidant activities, but its therapeutic potential for APAP hepatotoxicity remains unknown. This study aimed to assess the protective effects and mechanism of EsA against APAP-induced hepatotoxicity in vitro and in vivo. In vitro, EsA treatment inhibited APAP- or H2O2-induced cytotoxicity, H2O2 and O2- production, glutathione (GSH) depletion and apoptosis dependent on nuclear factor erythroid-2-related factor 2 (Nrf2) activation in HepG2 cells. Moreover, EsA significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and serine/threonine kinase (Akt), as well as glycogen synthase kinase 3 beta (GSK-3β) inhibitory phosphorylation at Ser9. Furthermore, an AMPK inhibitor (compound c) abolished the effects of EsA on AKT phosphorylation, GSK-3β inactivation, Nrf2 nuclear translocation and cytoprotection. With regard to APAP-induced acute liver injury, EsA attenuated the APAP-stimulated increases in the serum ALT and AST levels, as well as centrilobular necrosis and GSH depletion in the mice. In addition, it decreased the GSSG level, GSSG-to-GSH ratio, and the phosphorylation and mitochondrial translocation of c-Jun N-terminal kinase (JNK). Further, the protective potential of EsA against mitochondrial dysfunction was exhibited not only by inhibiting Bax mitochondrial translocation and the release of mitochondrial inter-membrane proteins, such as apoptosis-inducing factor (AIF), but also by activating Nrf2/HO-1. Collectively, our findings suggest that EsA has protective potential against APAP toxicity by potentiating the Nrf2-regulated survival mechanism through the AMPK/Akt/GSK3β pathway.
- Journal
- Free Radic Biol Med
- Publish Year
- 2016
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Acute Liver Failure
- Paper Title Cn
- Paper Title En
- Nrf2-mediated liver protection by esculentoside A against acetaminophen toxicity through the AMPK/Akt/GSK3β pathway
- Bilingual Status
- semi_complete