Abstract
BACKGROUND: Drug-induced liver injury (DILI) is the most common cause of acute liver injury. Anoectochilus roxburghii (Wall.) Lindl. (AR) and its polysaccharide fractions (ARPs) have been shown to have effective therapeutic effects with minimal side effects on a wide range of diseases including hepatopathy. This study aims to determine the therapeutic effects of ARPs on acetaminophen (APAP)-induced liver injury and to explore the mechanistic pathways involved. METHODS: C57BL/6J male mice at 8 weeks were used to construct a model of APAP-induced liver injury. The acute hepatic injury was induced by oral administration of APAP (300 mg/kg) before 16 h fasting. For therapeutic experiment, mice were gavaged with the water extract of AR (AR.WE) or the purified ARPs before and after APAP administration. Biochemical analyses, ELISA analyses, H&E staining, RT-PCR, and Quantitative proteomic analysis were used to investigate the effects and mechanisms of AR on DILI. RESULTS: Both AR.WE. and the purified ARPs treatment reduced APAP-induced liver injury, decreased hepatic glutathione and TNF-α levels, alleviated oxidative stress and inflammation. Quantitative proteomic analysis revealed that ARPs downregulated the protein levels involved in apoptosis, inflammation, oxidative stress, necroptosis, while upregulated the protein levels involved in autophagy. These protective effects of ARPs are possibly related to the downregulation of vATPase activity and thus participating in the autophagic process and ferroptosis. CONCLUSION: ARPs can protect mice against APAP-induced liver injury, alleviate oxidative stress and inflammation. Our study reveals a potential therapeutic effect for ARPs in protecting APAP-induced liver injury.