DataSheet3_Atractylenolide I Ameliorates Acetaminophen-Induced Acute Liver Injury via the TLR4/MAPKs/NF-κB Signaling Pathways.DOCX (76.8 kB)
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DataSheet3_Atractylenolide I Ameliorates Acetaminophen-Induced Acute Liver Injury via the TLR4/MAPKs/NF-κB Signaling Pathways.DOCX

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posted on 21.01.2022, 04:45 authored by Zhongyan Du, Zhimei Ma, Shanglei Lai, Qinchao Ding, Ziyi Hu, Wenwen Yang, Qianyu Qian, Linwensi Zhu, Xiaobing Dou, Songtao Li

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.

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