Flavor and Bioactive Component Dynamics in Pueraria lobata Fermentation and the Potential Hypolipidemic Mechanism: An Integrated Approach Combining Intelligent Sensory Analysis, UHPLC-QTOF/MS, Network Pharmacology, Molecular Docking and Dynamics Simulation

This study systematically investigated the multidimensional effects of lactobacillus fermentation on Pueraria lobata (PL), and preliminarily explored its differential mechanisms of lipid-lowering through variations in fermentation processes. Results indicate that lactobacillus fermentation effectively preserves the contents of pharmacologically active components such as total flavonoids and total phenols in PL, while promoting the accumulation of total acids and maintaining its inherent antioxidant capacity. Flavor analysis revealed enhanced astringency and attenuated bitterness in fermented PL, accompanied by the formation of volatile flavor compounds such as β-pinene and butyric acid trans-2-hexenyl ester, collectively contributing to its unique flavor profile. Non-targeted metabolomics reveals that lactobacillus fermentation specifically drives the enrichment of low-abundance isoflavone aglycones such as daidzein and genistein, which exhibit higher bioactivity and bioavailability with potential for enhanced hypolipidemic activity. Network pharmacology combined with computational simulation identified 8 key enriched compounds, including genistein, which stably bound to 10 core targets (e.g., MMP9, ESR1) via hydrogen bonds/hydrophobic interactions, activating phosphoinositide 3-kinase/protein kinase B(PI3K-AKT) and estrogen signaling pathways to regulate lipid metabolism. This study elucidates the the enzymatic hydrolysis of puerarin glycosides to aglycones mediated by lactobacillus fermentation, constructes a multidimensional network of "components-targets-pathways-hyperlipidemia," and provides theoretical support for developing functional Pueraria-derived lipid-lowering products.