Unveiling metabolome heterogeneity in three species from Coccoloba and Ruprechtia through multiple approaches of UPLC/HRMS and chemometric analysis in relation to antidiabetic, antioxidant and antiglycation activities

Abstract Background Diabetes mellitus (DM) is a major intricate metabolic disorder, being one of the chief causes of mortality worldwide. Coccoloba and Ruprechtia are two of the most intriguing polyphenol-rich genera within the Polygonaceae family. The potential of Coccoloba uvifera, Coccoloba peltata and Ruprechtia salicifolia total extracts and fractions as antioxidant, antidiabetic and anti-glycating agents was evaluated and correlated with their chemical composition via multiple approaches of metabolic profiling. Results All the total ethanolic extracts of plant leaves revealed remarkable antioxidant activities in terms of scavenging DPPH and ABTS radicals, as well as ferric reducing antioxidant power (FRAP). Despite having more or less comparable total phenolic and flavonoid contents, C. uvifera extract showed the highest inhibitory activity against α -glucosidase enzyme (IC 50 7.985 ± 1.08 μg/mL), being more potent than acarbose (20-fold). All total extracts demonstrated moderately high anti-AGEs (> 63% inhibition) in BSA-fructose model. Among all examined fractions, C. uvifera 50% MeOH fraction exhibited the most potent antioxidant activity in DPPH, ABTS and FRAP assays (5697.33 ± 360.7, 3078.9 ± 249, 1664.02 ± 220 µM ascorbic acid equivalent/mg extract, respectively) and the highest α -glucosidase inhibitory activity (IC 50 3.36 ± 1.04 μg/mL). A total of 140 compounds, belonging to different classes, were annotated in the three species via UPLC-HRMS, where flavonoids and phenolic acids represented the major classes. Multivariate and correlation analyses revealed the key phytochemicals contributing to α -glucosidase inhibition as 1- O -vanilloyl-hexoside, 1,3- O -diferuloylglycerol, drovomifoliol- O -glucopyranoside, protocatechuic acid glucoside, digalloyl glucose and coumaric acid sulphate. Conclusion C. uvifera leaves extract and its 50% MeOH fraction had a superb potential to alleviate DM and its complications through their antioxidant, antiglycation and α -glucosidase inhibitory activities mediated by their versatile polyphenolic phytochemicals. Graphical abstract