Gallotannin Isolated from Pericarp of Water Caltrop Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

Nonalcoholic fatty liver disease (NAFLD) is a worldwide prevalent chronic liver disease characterized by hepatic steatosis. Water caltrop, the fruit of Trapa natan, is widely cultivated as an edible vegetable in Asian countries. In China, water caltrop pericarp has long been used as a functional food to treat metabolic syndrome, yet the bioactive substances and their pharmacological mechanisms remain unclear. In this study, a natural gallotannin, 1,2,3,6-tetra- O -galloyl-β-D-glucopyranoside (GA), was isolated from water caltrop pericarp and evaluated for its therapeutic effect on NAFLD. Treatment of GA (15 and 30 mg/kg/day) suppressed the body weight gain ( p < 0.001) and ameliorated lipid deposition ( p < 0.001) in high-fat diet (HFD)-induced NAFLD mice. GA was able to alleviate HFD-induced insulin resistance ( p < 0.001), oxidative stress ( p < 0.001), and inflammation ( p < 0.001), thereby restoring the liver function in HFD-induced NAFLD mice. Mechanistically, GA diminished the aberrant signaling pathways including AMPK/SREBP/ACC, IRs-1/Akt, IKK/IκB/NF-κB in HFD-induced NAFLD mice and modified gut microbiota dysbiosis in these mice as well. The current findings suggest that GA is a promising novel agent for NAFLD therapy.