Optimal ratio of 18α- and 18β-glycyrrhizic acid for preventing alcoholic hepatitis in rats

The glycyrrhizic acid (GA) epimers 18α- and 18β-GA exert anti-inflammatory and hepatoprotective activities, which may help to protect against alcoholic liver disease, particularly alcoholic hepatitis (AH). The aim of the present study was to investigate the optimal ratio of 18α- and 18β-GA for preventing AH in rats. Different groups of rats were administered seven different ratios of 18α- and 18β-GA (10:0, 8:2, 6:4, 5:5, 4:6, 2:8 and 0:10; 10.83 mg/kg), vehicle control, or silymarin (22.75 mg/kg) as a positive control, followed by administration of 40% alcohol (10 ml/kg) once a day for four weeks. Subsequently, livers were isolated and routinely processed for histological examination. The serum levels of 23 cytokines and chemokines associated with AH were examined with a Bio-Plex 200 Luminex assay. It was revealed that all ratios of 18α- and 18β-GA prevented alcohol-induced liver injury, as evidenced by a lesser degree of histopathological changes in the liver as compared with those in the model group. Furthermore, the levels of 15 cytokines/chemokines were significantly altered after alcohol administration, which was significantly inhibited by, pre-treatment with different proportions of 18α- and 18β-GA, particularly at a ratio of 4:6, for most cytokines/chemokines associated with AH, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-7, IL-6, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-3α, macrophage- and granulocyte macrophage colony-stimulating factor, chemokine (C-X-C motif) ligand 1(GRO/KC), vascular endothelial growth factor and C-C motif chemokine ligand 5 (RANTES). Taken together, based on these results the optimal ratio of 18α- and 18β-GA to prevent AH in model rats was considered to be 4:6.