Isolation, Structural Characterization, and Hepatoprotective Activities of Isopentenylphenols from the Root Barks of <i>Glycyrrhiza uralensis</i>

Eight previously undescribed isopentenylphenols (glycyuralenins A-H, <b>1</b>-<b>8</b>) and seven known ones (<b>9</b>-<b>15</b>) were isolated from the root barks of <i>Glycyrrhiza uralensis</i>. Their structures were characterized by spectroscopic methods (MS, UV, and 1D and 2D NMR) and quantum chemical calculations. Compounds <b>1</b>-<b>3</b>, <b>5</b>, <b>7</b>, <b>8</b>, and <b>12</b> at 20 μM showed significant protective effects against acetaminophen (APAP)-induced AML12 cell injury. Among them, glycyuralenin A (<b>1</b>) was the most potent one, enhancing the cell viabilities to >90%. Moreover, <b>1</b> (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 <b>1</b> may inhibit the MAPK pathway through interactions with MAPK1 and MAPK8. These findings indicate the potential hepatoprotective applications of <b>1</b> and root bark extracts of <i>G. uralensis</i> in functional food and pharmaceutical products.