Isolation, Structural Characterization, and Hepatoprotective Activities of Isopentenylphenols from the Root Barks of Glycyrrhiza uralensis

Eight previously undescribed isopentenylphenols (glycyuralenins A-H, 1-8) and seven known ones (9-15) were isolated from the root barks of Glycyrrhiza uralensis. Their structures were characterized by spectroscopic methods (MS, UV, and 1D and 2D NMR) and quantum chemical calculations. Compounds 1-3, 5, 7, 8, and 12 at 20 mu M showed significant protective effects against acetaminophen (APAP)-induced AML12 cell injury. Among them, glycyuralenin A (1) was the most potent one, enhancing the cell viabilities to >90%. Moreover, 1 (25 mg/kg, i.g.) could significantly alleviate APAP-induced liver injury in mice by reducing liver necrosis and inflammation and decreasing serum levels of ALT and AST. Western blotting and molecular docking results revealed that 1 may inhibit the MAPK pathway through interactions with MAPK1 and MAPK8. These findings indicate the potential hepatoprotective applications of 1 and root bark extracts of G. uralensis in functional food and pharmaceutical products.