Diacerein protects liver against APAP-induced injury via targeting JNK and inhibiting JNK-mediated oxidative stress and apoptosis

• DOI: 10.1016/j.biopha.2022.112917
• Publication Date: 2022-04-04T10:00:43Z
• Authors: Mengyang Wang; Jinfeng Sun; Tianxiang Yu; Minxiu Wang; Leiming Jin; Shiqi Liang; Wu Luo; Yi Wang; Gao Li; Guang Liang
• Keywords: 0301 basic medicine; MAP Kinase Kinase 4; JNK Mitogen-Activated Protein Kinases; Anthraquinones; Apoptosis; 3. Good health; Mice, Inbred C57BL; Mice; Oxidative Stress; 03 medical and health sciences; Liver; Chemical and Drug Induced Liver Injury, Chronic; Hepatocytes; Animals; RNA; Chemical and Drug Induced Liver Injury; Acetaminophen

An overdose of acetaminophen (APAP) causes acute liver damage and lead to failure. Therefore, it is great clinical significance find drugs for the treatment APAP-induced injury. Diacerein clinically used drug osteoarthritis. Here, we evaluate pharmacological effects potential mechanisms diacerein in injury.C57BL/6 mice were treated with by gavage, followed intraperitoneal injection APAP (400 mg/kg) induce injury mice. RNA-sequencing analysis vitro kinase assay performed explore underlying diacerein. The experimental results showed that pretreatment could inhibit elevation serum AST ALT levels, hepatic histopathological damage, oxidative stress, hepatocyte death, mitochondrial indicated indicating JNK (c-Jun N-terminal kinase) involved liver-protective Diacerein. directly selectively phosphorylation cell-free system. We further confirmed inhibits APAP-activated pathway reduce response mouse livers cultured AML12 cells. Deficiency cells abolished anti-injury diacerein.Our suggest protects inhibition phosphorylation, rendering may serve as a therapeutic prevention