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.