Metabolomic insights into ultrasound-assisted fermentation of grape juice

Numerous studies have demonstrated that both lactic acid bacteria (LAB) fermentation and ultrasound-assisted fermentation can enhance the antioxidant activity of fruit juices; however, the effects of these two treatments on metabolites and antioxidant activity in grape juice (GJ) have yet to be investigated. Therefore, this study aimed to analyze the specific effects of LAB fermented grape juice (FGJ) and ultrasound-assisted fermented grape juice (UFGJ) on the antioxidant activity and metabolite production, while also conducting a preliminary investigation into the potential mechanisms underlying the antioxidant action of UFGJ using network pharmacology and molecular docking. The results indicated that UFGJ significantly enhanced the total phenolic content, total flavonoid content, and antioxidant activity of both FGJ and GJ (P < 0.001). Metabolomics analysis revealed highly significant differences in metabolite composition among the three groups (P < 0.001). The major differential metabolite classes and metabolic pathways of the FGJ versus GJ and UFGJ versus GJ groups were the same, with the latter group showing higher levels of shared metabolites. Thus, UFGJ does not alter the metabolic pathway of FGJ, but instead enhances its metabolic efficiency and increases metabolite enrichment. Correlation and network pharmacology analyses revealed that key antioxidant metabolites such as 2-hydroxycinnamic acid, gallic acid, and myricetin 3-rhamnoside primarily target core genes such as PPARG, EGFR, PTGS2, and PPARA, further regulating signaling pathways associated with chemical carcinogenesis-receptor activation, adherens junctions, and PPAR signaling pathway to exert antioxidant effects. Furthermore, molecular docking assays demonstrated that ursolic acid displaying the most stable binding to EGFR.