ReferenceID 1254
Atractylenolide I Ameliorates Acetaminophen-Induced Acute Liver Injury via the TLR4/MAPKs/NF-κB Signaling Pathways
Front Pharmacol
Background: Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), induces hepatocyte necrosis, and leads to acute liver failure. Atractylenolide I (AO-I), a phytochemical found in Atra
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
- 1254
- Evidence Id
- 17844
- Core Evidence Id
- 17844
- Source Reference Id
- 2497
- Herb2 Reference Id
- HBREF003294
- Subject Paper Key
- HBIN017285_35126160
- Pubmed Id
- 35126160
- Doi
- 10.3389/fphar.2022.797499
- Paper Title
- Atractylenolide I Ameliorates Acetaminophen-Induced Acute Liver Injury via the TLR4/MAPKs/NF-κB Signaling Pathways
- Paper Abstract
- Background: Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), induces hepatocyte necrosis, and leads to acute liver failure. Atractylenolide I (AO-I), a phytochemical found in Atractylodes macrocephala Koidz, is known to exhibit antioxidant activity. However, its clinical benefits against drug-induced liver injury remain largely unclear. Purpose: This study aimed at evaluating the protective effects of AO-I against APAP-induced acute liver injury. Methods: C57BL/6 mice were administered 500 mg/kg APAP to induce hepatotoxicity. AO-Ⅰ (60 and 120 mg/kg) was intragastrically administered 2 h before APAP dosing. Liver histopathological changes, oxidative stress and hepatic inflammation markers from each group were observed. Results: We observed that AO-I treatment significantly reversed APAP-induced liver injury, as evidenced by improved plasma alanine transaminase (ALT) level, aspartate aminotransferase (AST) and liver H&E stain. APAP treatment increased liver malondialdehyde (MDA) content and reduced catalase (CAT) and glutathione (GSH) level; however, these effects were alleviated by AO-I intervention. Moreover, AO-I treatment significantly inhibited APAP-induced activation of pro-inflammatory factors, such as IL-1β, IL-6, and TNF-α, at both the mRNA and protein levels. Mechanistic studies revealed that AO-I attenuated APAP-induced activation of TLR4, NF-κB and MAPKs (including JNK and p38). Conclusion: AO-I mediates protective effects against APAP-induced hepatotoxicity via the TLR4/MAPKs/NF-κB pathways. Thus, AO-I is a candidate therapeutic compound for APAP-induced hepatotoxicity.
- Journal
- Front Pharmacol
- Publish Year
- 2022
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Acute Liver Injury; Acute Liver Failure; Drug-induced Liver Injury; Hepatocyte Necrosis
- Paper Title Cn
- Paper Title En
- Atractylenolide I Ameliorates Acetaminophen-Induced Acute Liver Injury via the TLR4/MAPKs/NF-κB Signaling Pathways
- Bilingual Status
- semi_complete