Nonalcoholic fatty liver disease (NAFLD) has rapidly emerged as the most prevalent chronic liver disease globally, representing a significant and escalating public health challenge. Meconopsis integrifolia (Maxim.) Franch, a traditional Tibetan medicinal herb used for treating hepatitis, remains largely unexplored regarding its therapeutic potential and active components in combating NAFLD. This study first evaluated the in vitro lipid accumulation inhibitory activity of different extraction fractions of M. integrifolia using a HepG2 cell steatosis model. The ethyl acetate fraction was found to significantly reduce triglyceride (TG) and low-density lipoprotein (LDL) levels, inhibit lipid droplet deposition in HepG2 cells, and promote lipid metabolism balance through modulation of the AMPK/SREPB-1c/PPAR-α signaling pathway. Further analysis utilizing chromatographic techniques and nuclear magnetic resonance spectroscopy (NMR) led to the isolation of 13 compounds from the active ethyl acetate fraction. Notably, compounds 6, 9, 10, 11, 12, and 13 were identified for the first time from this Tibetan herb. In vitro activity assays and molecular docking analyses further confirmed that the compounds Luteolin (1), Quercetin 3-O-[2‴, 6‴-O-diacetyl-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (6), and Quercetin 3-O-[2‴-O-acetyl-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (8) are potential key components responsible for the NAFLD-ameliorating effects of M. integrifolia. This study highlights the therapeutic potential of M. integrifolia in treating NAFLD and provides a foundation for its further development and application, underscoring its significance in the advanced utilization of traditional Tibetan medicine.
Keywords: AMPK/SREPB-1c/PPAR-α signaling pathway; Meconopsis integrifolia (Maxim.) Franch; chemical constituents; molecular docking; non-alcoholic fatty liver disease.