Enzymatic synthesis and mechanistic insights into the hepatoprotective effects of α-monoglucosyl rutin against cyclophosphamide-induced liver injury: a multi-omics approach

Abstract

Rutin has attracted widespread attention due to its multiple pharmacological activities, but inherent defects such as poor water solubility and low bioavailability have greatly limited its clinical applications. Therefore, this study employed cyclodextrin glucanotransferase (CGTase) to catalyze the glycosylation modification of rutin, preparing rutin derivatives with improved water solubility. After optimizing the conditions, we isolated and purified 98.33 % of high-purity α-monoglucosyl rutin (α-GR), and its structure was also characterized. Subsequently, the cyclophosphamide (CTX)-induced murine liver injury model was used for activity evaluation. Our results showed that α-GR could significantly reduce liver function indicators (AST, ALT, and TBA), regulate antioxidant enzyme activities and inflammatory factor levels, and effectively attenuate CTX-induced liver injury. Furthermore, integrated metabolomics, transcriptomics, and RT-PCR analyses indicated that α-GR primarily exerts its hepatoprotective effects by intervening in key metabolites and gene expressions in CTX metabolic processes, related inflammatory responses, and oxidative stress pathways. Our results show that α-GR can effectively repair liver damage caused by CTX, thus laying the foundation for its use as a dietary supplement or therapeutic adjuvant.