ReferenceID 5913
Oridonin ameliorates acetaminophen-induced acute liver injury through ATF4/PGC-1α pathway
Drug Dev Res
Acetaminophen (APAP) overdose-induced acute liver injury (ALI) causes hepatocyte cell death, oxidative stress, and inflammation. Oridonin (Ori), a covalent NLRP3-inflammasome inhibitor, ameliorates APAP-induced ALI throu
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 5913
- Evidence Id
- 22503
- Core Evidence Id
- 22503
- Source Reference Id
- 5082
- Herb2 Reference Id
- HBREF005879
- Subject Paper Key
- HBIN038254_36567664
- Pubmed Id
- 36567664
- Doi
- 10.1002/ddr.22024
- Paper Title
- Oridonin ameliorates acetaminophen-induced acute liver injury through ATF4/PGC-1α pathway
- Paper Abstract
- Acetaminophen (APAP) overdose-induced acute liver injury (ALI) causes hepatocyte cell death, oxidative stress, and inflammation. Oridonin (Ori), a covalent NLRP3-inflammasome inhibitor, ameliorates APAP-induced ALI through an unclear molecular mechanism. This study found that Ori decreased hepatic cytochrome P450 2E1 level and increased glutathione content to prevent APAP metabolism, and then reduced the necrotic area, improved liver function, and inhibited APAP-induced proinflammatory cytokines and oxidative stress. Ori also decreased activating transcription factor 4 (ATF4) protein levels and increased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) to reduce APAP-induced endoplasmic reticulum stress activation and mitochondrial dysfunction. Furthermore, western blot and luciferase assay found that ATF4 inhibited transcription in the PGC-1α promoter -507 to -495 region to reduce PGC-1α levels, while ATF4 knockdown neutralized the hepatoprotective effect of Ori. Molecular docking showed that Ori bound to ATF4's amino acid residue glutamate 302 through 6, 7, and 18 hydroxyl bands. Our findings demonstrated that Ori prevented metabolic activation of APAP and further inhibited the ATF4/PGC-1α pathway to alleviate APAP overdose-induced hepatic toxicity, which illuminated its potential therapeutic effects on ALI.
- Journal
- Drug Dev Res
- Publish Year
- 2022
- Experiment Subject
- Experiment Type
- Animal Experiment
- Phenotype Related
- Acute Liver Injury; Inflammation; Hepatocyte Cell Death; Mitochondrial Dysfunction
- Paper Title Cn
- Paper Title En
- Oridonin ameliorates acetaminophen-induced acute liver injury through ATF4/PGC-1α pathway
- Bilingual Status
- semi_complete