Antihyperglycemic activity and bioguided isolation of phenolic compounds with antioxidant and cytotoxic properties from Syzygium malaccense leaves

This study investigated the antihyperglycemic potential of a hydroalcoholic extract from Syzygium malaccense leaves (E-SM) and isolate phenolic compounds with antioxidant and cytotoxic activities through a bioguided assay. The aim was to explore the therapeutic properties of S. malaccense in managing hyperglycemia and oxidative stress-related conditions. E-SM was prepared using ethanol-water (40:60 v/v) and purified through a solid-liquid procedure with increasing polarity solvents, yielding the acetone fraction (AceFr). Previous studies showed Ace-Fr had potent antioxidant and cytotoxic properties. Chromatographic techniques further purified AceFr, producing three bioactive subfractions (SF-1, SF-2, and SF-3). Flavonoids myricitrin (C1) and a mixture of quercitrin and mearnsitrin (M1) were isolated from SF-2 and SF-3 using TLC preparative. HPLC-DAD quantified phenolic compounds, including myricitrin, gallic acid, myricetin, and quercetin. HPLC-ESI-QTOF-MS/MS analysis identified ten compounds, primarily flavonols quercetin and myricetin and their glycosides. SF-1 exhibited a 30 % reduction in cell viability in cutaneous melanoma cells at 100 and 250 mg L^-1, while SF-2 and SF-3 displayed enhanced antioxidant potential and reduced cancer cell locomotion proportional to concentration. In diabetic rats treated with E-SM (400 mg/kg), kidney tissue showed restored catalase activity similar to the control group, with consistent NPSH levels. Increased GST activity indicated tissue protection, while lower MDA levels suggested reduced lipid peroxidation across tissues. Our results indicate that three phenolic compounds with high antioxidant activity were isolated, and the chemical composition of the E-SM extract, rich in glycosylated flavonoids, could be related to its antihyperglycemic action.