DataSheet3_Atractylenolide I Ameliorates Acetaminophen-Induced Acute Liver Injury via the TLR4/MAPKs/NF-κB Signaling Pathways.DOCX
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.
History
References
- https://doi.org//10.1016/j.fct.2018.08.060
- https://doi.org//10.7150/thno.43894
- https://doi.org//10.1002/ctm2.324
- https://doi.org//10.1111/exd.13454
- https://doi.org//10.1016/j.bcp.2020.114344
- https://doi.org//10.1002/hep.29153
- https://doi.org//10.1016/j.foodchem.2013.03.061
- https://doi.org//10.1016/j.molmed.2007.09.002
- https://doi.org//10.1016/j.cld.2007.06.006
- https://doi.org//10.1101/cshperspect.a001651
- https://doi.org//10.1016/j.jhep.2017.07.005
- https://doi.org//10.1002/ptr.6160
- https://doi.org//10.1002/ptr.2040
- https://doi.org//10.1016/j.bbalip.2013.09.004
- https://doi.org//10.1016/j.intimp.2015.02.002
- https://doi.org//10.1053/j.gastro.2004.08.053
- https://doi.org//10.1172/JCI26322
- https://doi.org//10.1016/j.phymed.2020.153241
- https://doi.org//10.1016/j.jhep.2004.09.015
- https://doi.org//10.3389/fphar.2021.752148
- https://doi.org//10.1007/s00018-014-1762-5
- https://doi.org//10.1002/JLB.5A1119-279R
- https://doi.org//10.1016/j.intimp.2020.106292
- https://doi.org//10.1016/j.phymed.2017.03.001
- https://doi.org//10.1097/00007890-199306000-00011
- https://doi.org//10.1016/j.smim.2003.10.003
- https://doi.org//10.1016/j.apjtm.2017.06.007
- https://doi.org//10.1016/j.taap.2021.115817
- https://doi.org//10.4268/cjcmm20121224
- https://doi.org//10.1080/15548627.2016.1187365
- https://doi.org//10.1155/2019/1875471
- https://doi.org//10.3390/antiox8090395
- https://doi.org//10.3389/fphar.2020.601716
- https://doi.org//10.1038/s41419-020-2334-2
- https://doi.org//10.1016/j.redox.2018.04.019
- https://doi.org//10.1016/j.phymed.2020.153211
- https://doi.org//10.1007/s13181-018-0653-9
- https://doi.org//10.1002/hep.23476
- https://doi.org//10.1007/s00253-017-8686-6
- https://doi.org//10.1016/j.ejphar.2015.08.022
- https://doi.org//10.1016/j.cbi.2016.03.008
- https://doi.org//10.1007/s12192-019-00993-1
- https://doi.org//10.1016/j.phrs.2019.02.016
- https://doi.org//10.1002/hep4.1757
- https://doi.org//10.1111/1440-1681.13306
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