The novel contributors of anti-diabetic potential in mulberry polyphenols revealed by UHPLC-HR-ESI-TOF-MS/MS

•Mulberry polyphenols were fractionated through gradient ethanol elution.•UHPLC-MS/MS identified and quantified 47 phenolic compounds, including 21 new ones.•Antioxidant activity and anti-diabetic potential were analyzed in vitro & ex vivo.•Hierarchical cluster and correlation analysis reveal contributors to bioactivities.•Dihydroquercetin & 1,5-dicaffeoylquinic acid contribute to anti-diabetic potential.

To explore the comprehensive phenolic profile of mulberry (Morus alba L.) fruit and reveal the novel anti-diabetic constituents, mulberry polyphenols (MP) were fractionated through gradient ethanol elution and subjected to composition and bioactivity analysis. Forty-seven phenolic compounds were identified and quantified through UHPLC-HR-ESI-TOF-MS/MS, including twenty-one newly identified compounds such as delphinidin 3-rutinoside-5-glucoside and cyanidin 3-rutinoside dimer. The antioxidant activity and anti-diabetic potential of fractionated MP were analyzed in vitro and ex vivo with HepG2 and pancreatic β-cell RIN-m5F. Hierarchical cluster analysis and Pearson correlation coefficients revealed compounds such as syringic acid and galloylcyanidin-glycoside contributed most to inhibit α-glucosidase activity. Quercetin and cyanidin-glycosides were essential for cellular antioxidant activity. Dihydroquercetin and 1,5-dicaffeoylquinic acid were newly identified and validated as the main contributors after rutin to protect RIN-m5F cells against glucotoxicity. Such findings suggest the promising role of MP for type II diabetics and lay the foundation of further utilization and investigation.

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