ReferenceID 2540

Oroxylin a promotes PGC-1α/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease

Free Radic Biol Med

BACKGROUND: It is well acknowledged that alcoholic liver disease (ALD) is widely prevalent all over the world, characterized by aberrant lipid deposition and excessive oxidative stress in hepatocytes. Recently, pyroptosi

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Reference Id
2540
Evidence Id
19130
Core Evidence Id
19130
Source Reference Id
5087
Herb2 Reference Id
HBREF005884
Subject Paper Key
HBIN038303_32289481
Pubmed Id
32289481
Doi
10.1016/j.freeradbiomed.2020.03.031
Paper Title
Oroxylin a promotes PGC-1α/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease
Paper Abstract
BACKGROUND: It is well acknowledged that alcoholic liver disease (ALD) is widely prevalent all over the world, characterized by aberrant lipid deposition and excessive oxidative stress in hepatocytes. Recently, pyroptosis, a new type of programmed cell death, has been found in ALD, which provides new ideas for the treatment of ALD. METHODS: Male ICR mice were treated with the Lieber-De-Carli diet (Dyets) or isocaloric liquid diet for 8 weeks, and binge alcohol model was also used for ALD. Blood and livers were taken to evaluate the efficacy of oroxylin A. The levels of factors related to hepatocyte pyroptosis were measured via western blot analyses, immunofluorescence analyses and quantitative reverse transcriptase in vitro. RESULT: Our study found that oroxylin A suppressed hepatocyte pyroptosis through a NLRP3 inflammasome dependent-canonical caspase-1 pathway. Results illuminated that oroxylin A inhibited NLRP3 inflammasome activation by reducing ROS accumulation. Furthermore, oroxylin A upregulated mitofusin 2 (Mfn2) to resist lipid deposition and mitochondria-derived ROS overproduction. As an upstream mediator of Mfn2, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha), a major regulator of mitochondria, was found to promote transcription of Mfn2 under oroxylin A treatment. CONCLUSION: Our research revealed that oroxylin A could alleviate ALD via PGC-1alpha/Mfn2 signaling mediated canonical pyroptosis pathway resistance.
Journal
Free Radic Biol Med
Publish Year
2020
Experiment Subject
mouse
Experiment Type
Animal & Cell Experiment
Phenotype Related
Alcoholic Liver Disease; Pyroptosis
Paper Title Cn
Paper Title En
Oroxylin a promotes PGC-1α/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease
Bilingual Status
semi_complete