Abstract

Background An overdose of acetaminophen (APAP), the main cause of acute liver failure (ALF), induces oxidative stress that ultimately causes mitochondrial impairment and hepatotoxicity . The nuclear factor erythroid 2-related factor 2 (Nrf2) was widely recognized as an anti-oxidative stress mechanism. The present study was aimed at investigating whether sarmentosin, extract from traditional Chinese medicine, protects the liver against APAP-induced injury via activating Nrf2 and subsequently decreasing oxidative stress. Methods Male ICR mice were treated with sarmentosin oral administration for 1 week and injected APAP (300 mg/kg. i.p.) for acute liver injury model. The liver and serum of mice for histological and biochemistry analysis. AML12 and LO2 cells were used in vitro assays. Results We found that sarmentosin moderately increased accumulation of Nrf2 via upregulating USP17-mediated ubiquitin inhibition at the early stage of hepatocytes damage. The Nrf2 separating from bonding protein Keap1 translocated into nucleus and activated downstream gene of antioxidants. Mitophagy , a unique autophagy can remove Reactive Oxygen Species (ROS) damaged mitochondria, was elevated in this progress to maintain mitochondria function and ROS homeostasis . Conclusion In summary, our research revealed that sarmentosin could alleviate APAP-induced liver acute injury through USP17-mediated Nrf2 overexpression and PINK1-dependent mitophagy.