Synergistic Enhancement of Antioxidant and Cytoprotective Activities in Lonicerae Japonicae Flos via Co-fermentation: Metabolomics Unraveling Key Biotransformation Pathways

ABSTRAT Lonicera japonica is a medicinal food rich in polyphenols. However, most of the polyphenols are in the bound state, thus resulting in low extraction efficiency. In this study, the antioxidant and cytoprotective activities of L. japonica were improved after fermentation, through metabolomics, it was found that the level of some polyphenols increased, which revealed the reason for the enhanced antioxidant and cytoprotective activities of L. japonicum after fermentation. Results showed that the ·OH scavenging rate of Picp-2 and co-fermentation groups increased of 23% and 13%, the DPPH· scavenging rate of SY group increased of 10%, and the cytoprotection activity of co-fermentation group increased of 32%. Besides, metabolomics based on LC/MS identified a total of 576, 358, 651 differential metabolites in Picp-2, SY and co-fermentation groups respectively. The levels of benzoic acids, coumaric acids, cinnamic acids, fatty acids and flavonoids in Picp-2 and SY groups significantly increased. The Picp-2 group separately detected the increase of amino acids, quinic acids, terpene glycosides, and catechin. The changes of metabolites level in co-fermentation group were similar to the single strain groups, while the change fold was smaller. Moreover, the correlation analysis revealed a significantly positive correlation between the contend of demethyltexasin, ferulic acid, chlorogenic acid, and eriodictyol with antioxidant activity. Additionally, the amount of taxifolin, paeonol, and riboflavin were significantly positively correlated with cytoprotection activity. This study is the first to find that co-fermentation with Lactiplantibacillus plantarum and Saccharomyces cerevisiae could improve the cytoprotective activity of L. lonicerae , and revealed the potential biotransformation pathway of active substances through metabolomics.