Objective To investigate the detoxification effect of carnosic acid(CA), a natural phenolic acid compound, on liver injury induced by Rhizoma Dioscoreae Bulbiferae and to explore its potential mechanism.

Methods Male KM mice were randomly divided into 6 groups (n = 8 per group): control group (0.5% CMC-Na solution), model group (ethanol extract of Rhizoma Dioscoreae Bulbiferae), silymarin group (silymarin + ethanol extract of Rhizoma Dioscoreae Bulbiferae), and low-, medium-, and high-dose CA groups (different doses of CA + ethanol extract of Rhizoma Dioscoreae Bulbiferae). The mice were intragastrically administered for 14 consecutive days, and their food intake, water intake and body weight were recorded. After the end of the experiment, body weight and liver mass of the mice were weighed, and liver index was calculated. The expression levels of plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (T-BIL), superoxide dismutase (SOD) activity, catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) were determined. Western blotting was used to detect the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA expression of multidrug resistance-associated protein 2 (MRP2), bile salt export pump (BSEP), and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of liver tissues.

Results Compared with the model group, CA reduced liver weight and liver index in mice, decreased plasma levels of AST, ALT, ALP, and T-BIL, increased plasma levels of SOD, CAT, and GSH, and decreased MDA levels. It upregulated the protein expression of Nuc-Nrf2 and HO-1, inhibited the protein expression of p-NF-κB p65, TNF-α, and IL-6, and promoted increases in the mRNA expression of MRP2, P-gp, BSEP, and UGT1A1 (all P ＜ 0.05). The results of HE staining showed that CA reduced inflammatory infiltration and necrosis of hepatocytes and ameliorated hepatocellular structural damage.

Conclusion CA may exert a detoxification effect against Rhizoma Dioscoreae Bulbiferae-induced liver injury by activating the Nrf2 regulatory pathway and its downstream key indicators.