Abstract: 【Objective】 The aim of this experiment was to investigate the protective effect of puerarin (PU) on acetaminophen (APAP)-induced acute liver injury in mice, and provide a new idea for the clinical prevention and treatment of liver injury caused by APAP.【Method】 Forty 4-week-old SPF-grade male Kunming mice weighing (20±2) g were randomly divided into four groups:Normal (CON), model (APAP), puerarin low-dose (L-PU), and puerarin high-dose (H-PU) groups, 10 mice in each group.Mice were kept normally in CON group, and mice in L-PU and H-PU groups were gavaged with 50 and 100 mg/kg puerarin, respectively, once daily for 7 days.After the last administration, the mice in APAP, L-PU and H-PU groups were fasted for 16 h and gavaged with 200 mg/kg acetaminophen once.Continue fasting for 12 h, blood was collected from the orbit after anesthesia, and the mice were killed after cervical dislocation.The liver was quickly collected, and the liver morphology was observed and the liver index was calculated.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured to evaluate the liver injury.The liver catalase (CAT) activity and total antioxidant capacity (T-AOC) were determined to evaluate the liver oxidative stress.The levels of glutathione S-transferase (GST) and cytochrome P450 family 2 subfamily E member 1 (cytochrome P450 2E1, CYP2E1) were measured to analyze the metabolism of APAP in liver.The apoptosis-related protein cysteine protease caspase-3 and caspase-9 levels were determine to evaluate the apoptosis of liver cells.The pathological sections of the liver were made and the histological changes of the liver were observed after HE staining.【Result】 Compared with CON group, the liver in APAP group was hard with obvious bleeding, the liver tissue structure was severely damaged, the hepatic cords were disordered, the structure of the liver lobules was not clear, and there was massive necrosis of hepatocytes, the liver index and ALT and AST levels in serum were significantly increased (P<0.05), the activity of CAT, T-AOC and GST level were significantly decreased (P<0.05), and the contents of apoptotic proteins caspase-3, caspase-9 and CYP2E1 were significantly increased (P<0.05).Compared with APAP group, the liver morphology and tissue structure of L-PU and H-PU groups were basically normal, and the effect of H-PU group was more significant.In L-PU and H-PU groups, the liver index and the activities of AST and ALT in serum were significantly decreased (P<0.05), CAT activity and T-AOC in liver were significantly increased (P<0.05), and the level of caspase-9 was significantly decreased (P<0.05).In addition, L-PU and H-PU groups increased the level of GST and significantly decreased the level of CYP2E1 (P<0.05).【Conclusion】 The significant protective effect of puerarin on APAP-induced liver injury in mice might be related to the antioxidant, anti-apoptotic, and accelerated APAP detoxification effects of puerarin.

Key words: puerarin; acetaminophen; drug induced liver injury