Uncovering the phytochemical diversity and anti-diabetic potential of Rubus suavissimus leaf using conventional and novel extraction strategies.

The rising global prevalence of type 2 diabetes (T2D) necessitates the development of safe and cost-effective alternatives to pharmacotherapies. This study comprehensively investigated the phytochemical profile and anti-diabetic activity of R. suavissimus leaf extracts prepared using conventional and novel extraction methods. Untargeted metabolomics revealed a diverse phytochemical profile dominated by flavonoids, phenolic acids, and ellagitannins including corilagin and castanin identified as major ones for the first time. Chemometric analysis further revealed that high hydrostatic pressure-assisted extraction and ultrasound-assisted extraction outperformed conventional extraction in enriching phytochemicals, particularly polyphenol glycosides and ellagitannins. The extracts exerted dual anti-diabetic actions through potent α-glucosidase inhibition and insulin secretion stimulation in INS-1E β-cells, with extracts prepared by ethanol-based novel strategies showing superior efficacy. Molecular docking and network pharmacology further revealed synergistic and multi-target mechanisms involving α-glucosidase inhibitory and insulin-signaling modulating activities. Our findings lay the groundwork for development of R. suavissimus-based products for metabolic health promotion.