Exploring the Nutraceutical Potential of a Food–Medicine Compound for Metabolic-Associated Fatty Liver Disease via Lipidomics and Network Pharmacology

Metabolic-associated fatty liver disease (MAFLD) is a prevalent global health issue closely tied to dietary habits, impacting a significant portion of the adult population. MAFLD is linked to various metabolic disorders, elevating risks of cirrhosis and hepatocellular carcinoma and severely impacting patients’ quality of life. While therapeutic research has progressed, effective food-based interventions remain scarce. Natural products, rich in bioactive compounds and offering health benefits, have gained attention for their potential in managing MAFLD. This study employed network pharmacology and lipidomics to investigate the therapeutic effects of Food and Medicine Homology (FMH) on MAFLD using a high-fat-diet-induced HepG2 cell model. We identified 169 potential bioactive components from Radix Puerariae, Hericium erinaceus, Rhizoma Curcumae longae, Camellia oleifera, and Hoveniae Dulcis Semen, constructing a drug–component–target network that highlighted 34 key targets. The characteristic components of this FMH compound solution (HSD) were identified using UPLC-QTOF-MS/MS. In vitro, HSD significantly reduced intracellular lipid accumulation, decreased inflammatory markers, and mitigated hepatocyte damage. Lipidomics analysis revealed significant alterations in lipid metabolites, suggesting HSD’s potential to modulate sphingolipid and glycerophospholipid metabolism, thus improving MAFLD outcomes. This research underscores the critical role of the FMH complex in modulating lipid metabolism and inflammatory pathways, offering valuable insights for developing FMH-based dietary supplements and functional foods to alleviate MAFLD. By leveraging the synergistic effects of natural compounds, our findings hold significant implications for innovative nutritional strategies in managing this prevalent metabolic disorder.