Bioactive aporphines and flavonoids from a fermented beverage target metabolic inflammatory pathways in obesity and...

The global syndemic of obesity and type 2 diabetes (T2D) demands safe, multi-targeted dietary interventions. FH03FS, a sterilized fermented beverage blended from five medicinal food homologous (MFH) plants, represents a promising candidate. However, the phytochemical profile and mechanistic basis for its potential efficacy remain uncharacterized. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis of FH03FS revealed a wide spectrum of compounds. Ten key bioactive ingredients, primarily aporphines and flavonoids, were identified as the primary active components based on favorable pharmacokinetic properties. In silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling indicated high gastrointestinal (GI) absorption and low toxicity risks for these compounds. Network pharmacology demonstrated the modulation of core pathways driving metabolic inflammation. Molecular docking preliminarily identified multiple high-affinity interactions between the bioactive compounds and core targets. The exceptional stability and strong binding of representative complexes, notably Morin-ESR1 and Asimilobine-PPARG, were further validated by molecular dynamics (MD) simulations. This study demonstrates that FH03FS, rich in aporphines and flavonoids, exerts multi-target effects against obesity and T2D. Our findings thereby provide a phytochemical and mechanistic foundation for its development as a ready-to-consume functional beverage and offer testable hypotheses for future validation.