High Dihydromyricetin Loaded Biomimetic Nanoemulsion Ameliorated Early Nonalcoholic Fatty Liver Disease by Hepatic Ferroptosis Inhibition

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by lipid accumulation in the liver, and is often linked to ferroptosis, an iron-dependent programmed cell death driven by lipid peroxidation. Dihydromyricetin (DMY), a flavonoid from Ampelopsis grossedentata, exhibits anti-NAFLD efficiency but has low bioavailability. In this study, a high DMY-loaded biomimetic nanoemulsion (DMY-bNE) was developed using a double emulsification method with glyceryl monooleate. Methods: DMY-bNE was characterized in vitro and in vivo including encapsulation efficiency (EE), drug-loading capacity (DLE), gastrointestinal (GI) absorption, biodistribution, pharmacokinetics, safety. High fat diet induced NAFLD mouse model was used to investigate the therapeutic effect and mechanism. Results: DMY-bNE showed high EE (99.5%) and DLE (24.9%), promoted GI absorption, enhanced liver accumulation, improved pharmacokinetic properties and good in vivo safety. In NAFLD mice, DMY-bNE significantly ameliorated the disease progression by inhibiting hepatic ferroptosis. Conclusion: These findings demonstrated that DMY-bNE combines enhanced drug delivery with ferroptosis inhibition, thereby offering a promising strategy for NAFLD therapy.