Abstract: 【Objective】 The aim of this study was to explore the protective effect of self-constituted prescription Zhen-Ju decoction on mice with acute liver injury caused by three different causative factors.【Method】 The main components and contents of Zhen-Ju decoction were determined by high-performance liquid chromatography (HPLC).The antioxidant and anti-inflammatory effects of Zhen-Ju decoction were investigated using 1, 1-diphenyl-2-picrylhydrazyl radical(DPPH) scavenging rate, hydroxyl radical scavenging rate, total reducing capacity and inhibition of 5-lipoxygenase(5-LOX) activity.42 mice were randomly divided into 7 groups to perform 24 h oral acute toxicity test and 21 d accumulation toxicity test to evaluate its safety.An additional 113 mice were selected, of which 8 were randomly selected as the blank control group (Control), and the remaining 105 were randomly assigned equally to three drug-induced acute liver injury trials, with 35 mice in each trial.Each acute liver injury test group was randomly divided into Model group, positive drug Silybum marianum group (Silybin) and high, medium and low dose Zhen-Ju decoction groups, with 7 rats in each group.Control and Model groups were oral administrated with saline for 14 d, Silybin group was oral administrated with 50 mg/kg Silybin for 14 d, the high, medium, and low dose groups were oral administrated with 10.0, 5.0, and 2.5 g/kg of Zhen-Ju decoction for 14 d, respectively. On the 15th day, acute liver injury models were induced with carbon tetrachloride (CCl₄), acetaminophen (APAP), and alcohol (Alcohol), respectively. Mice were executed at 16 or 20 d, then detected changes in liver pathology, serum biochemical parameters, antioxidant parameters, inflammatory factors and liver-specific gene miRNA (miR-122).【Result】 According to the determination by HPLC, each 1 g of Zhen-Ju decoction formula contained 0.27 mg of rutin, 2.72 mg of lignan, 0.26 mg of isochlorogenic acid A and 0.28 mg of berberine hydrochloride.The DPPH radical scavenging half maximal inhibitory concentration(IC₅₀) and hydroxyl radical scavenging IC₅₀ of Zhen-Ju decoction were 2.394 and 104 mg/mL, respectively, with a total reducing capacity of 3.73±0.04 and an anti-inflammatory rate of 75.97%±3.11%.The oral acute toxicity test and accumulation toxicity test showed that Zhen-Ju decoction was safe and non-toxic.In the pathological model of acute liver injury caused by CCl₄, APAP and Alcohol, the liver tissues of mice in Model group showed different degrees of lesions, and different doses of Zhen-Ju decoction and positive drug Silybin group showed some degree of improvement.Compared with Model group, after the high-dose intervention of Zhen-Ju decoction, the liver serum biochemical indicators glutamic oxalyl transaminase (AST), glutamic alanine transaminase (ALT), triglyceride (TG) and total cholesterol (T-CHO) were significantly lower (P<0.05), the antioxidant index malondialdehyde (MDA) was significantly lower (P<0.05) and superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) were significantly higher (P<0.05), the inflammatory factors interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) and miR-122 were significantly lower (P<0.05).【Conclusion】 Zhen-Ju decoction was a safe and non-toxic formula, and oral administrated with 10.0 g/kg Zhen-Ju decoction could significantly improve liver lesions and increase the antioxidant capacity of mouse liver, and had a good protective effect against acute liver injury caused by CCl₄, APAP and Alcohol.

Key words: Zhen-Ju decoction; acute liver injury; antioxidant; anti-inflammatory; miR-122