Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway

• Main Authors: Licong Zhao (Author), Jiaqi Zhang (Author), Cheng Hu (Author), Tao Wang (Author), Juan Lu (Author), Chenqu Wu (Author), Long Chen (Author), Mingming Jin (Author), Guang Ji (Author), Qin Cao (Author), Yuanye Jiang (Author)
• Format: Book
• Published: Frontiers Media S.A., 2020-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2020.00514
• Keywords: apigenin; acetaminophen-induced liver injury; SIRT1 pathway; flavonol; antioxidant; SIRT1-p53 axis; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 11 (2020)

Acetaminophen (APAP) overdose is the main cause of acute liver failure. Apigenin (API) is a natural dietary flavonol with high antioxidant capacity. Herein, we investigated protection by API against APAP-induced liver injury in mice, and explored the potential mechanism. Cell viability assays and mice were used to evaluate the effects of API against APAP-induced liver injury. Western blotting, immunofluorescence staining, RT-PCR, and Transmission Electron Microscope were carried out to determine the signalling pathways affected by API. Analysis of mouse serum levels of alanine/aspartate aminotransferase (ALT/AST), malondialdehyde (MDA), liver myeloperoxidase (MPO) activity, glutathione (GSH), and reactive oxygen species (ROS) revealed that API (80 mg/kg) owned protective effect on APAP-induced liver injury. Meanwhile, API ameliorated the decreased cell viability in L-02 cells incubated by APAP with a dose dependent. Furthermore, API promoted SIRT1 expression and deacetylated p53. Western blotting showed that API promoted APAP-induced autophagy, activated the NRF2 pathway, and inhibited the transcriptional activation of nuclear p65 in the presence of APAP. Furthermore, SIRT1 inhibitor EX-527 reduced protection by API against APAP-induced hepatotoxicity. Molecular docking results indicate potential interaction between API and SIRT1. API prevents APAP-induced liver injury by regulating the SIRT1-p53 axis, thereby promoting APAP-induced autophagy and ameliorating APAP-induced inflammatory responses and oxidative stress injury.