Co-analysis of network pharmacology and metabolomics: revealing the mechanism of using mixed strains to produce multi-stage fermentation products of fresh blue honeysuckle (Lonicera caerulea L.) to against hyperlipidemia

This study systematically investigated the molecular mechanism of the physicochemical properties, bioactive compound spectrum, and lipid-lowering activity of fermented Lonicera caerulea L. juice (FLJ) by sequential fermentation of compound lactic acid bacteria and yeast. The results indicated that compared to other methods, the sequential fermentation strategy (SFL Y) could significantly enhance the levels of bioactive substances (flavonoids, SOD enzyme) and lipid-lowering activity. Using LC-MS techniques, 193 differential metabolites were detected after fermentation, including changes in 14 major chemical components such as organic acids, amino acids, and flavonoids. In addition, phenylpropanoid biosynthesis and linoleic acid metabolism were the core pathways in the SFL-Y fermentation process. Regarding lipid-lowering activity, network pharmacology and molecular docking validated the interaction between key metabolites (9,10-epoxylinoleic acid, 9,10-DHOME) and hyperlipidemia targets (CXCL8, IL1B, MAPK14), elucidating their molecular mechanisms of lipid-lowering. This study provides a theoretical basis for developing functional fermented beverages through microbial community synergy and metabolic regulation. • Multi-stage fermentation can improve the quality of Lonicera caerulea L. products. • The inoculation sequence of strains has a significant impact on fermentation. • CXCL8, IL1B, and MAPK14 have good binding ability with 9,10-epoxyoctadecenoic acid. • LAB and yeast may effect the biosynthesis of linoleic acid metabolism.