Annona muricata Linn. leaf as a source of antioxidant compounds with in vitro antidiabetic and inhibitory potential against α-amylase, α-glucosidase, lipase, non-enzymatic glycation and lipid peroxidation.

Annona muricata leaves are used in traditional medicine to manage diabetes mellitus and its complications. The aim of this study was to evaluate the potential in vitro antidiabetic properties of Annona muricata leaf by identifying its main phytochemical constituents and characterizing the phenolic-enriched fractions for their in vitro antioxidant capacity and inhibitory activities against glycoside and lipid hydrolases, advanced glycation end-product formation and lipid peroxidation. Ethanol extract of A. muricata leaf was subjected to a liquid-liquid partitioning and its fractions were used in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant (DPPH, ORAC, FRAP and Fe2+-ascorbate-induced lipid peroxidation assays) and anti-glycation (BSA-fructose, BSA-methylglyoxal and arginine-methylglyoxal models) capacities. In addition, identification of the main bioactive compounds of A. muricata leaf by HPLC-ESI-MS/MS analysis was carried out. Ethyl acetate (EtOAc) and n-butanol (BuOH) fractions showed, respectively, antioxidant properties (ORAC 3964 ± 53 and 2707 ± 519 μmol trolox eq g-1, FRAP 705 ± 35 and 289 ± 18 μmol trolox eq g-1, and DPPH IC50 4.3 ± 0.7 and 9.3 ± 0.8 μg mL-1) and capacity to reduce liver lipid peroxidation (p < .01). Also, EtOAc and BuOH, respectively, inhibited glycation in BSA-fructose (IC50 45.7 ± 13.5 and 61.9 ± 18.2 μg mL-1), BSA-methylglyoxal (IC50 166.1 ± 21.6 and 413.2 ± 49.5 μg mL-1) and arginine-methylglyoxal (IC50 437.9 ± 89.0 and 1191.0 ± 199.0 μg mL-1) assays, α-amylase (IC50 9.2 ± 2.3 and 6.1 ± 1.6 μg mL-1), α-glucosidase (IC50 413.1 ± 121.1 and 817.4 ± 87.9 μg mL-1) and lipase (IC50 74.2 ± 30.1 and 120.3 ± 50.5 μg.mL-1), and presented lower cytotoxicity, when compared to the other fractions and crude extract. Various biomolecules known as potent antioxidants were identified in these fractions, such as chlorogenic and caffeic acids, procyanidins B2 and C1, (epi)catechin, quercetin, quercetin-hexosides and kaempferol. This study presents new biological activities not yet described for A. muricata, which contributes to the understanding of the potential effectiveness in the use of the A. muricata leaf, especially its polyphenols-enriched fractions, for the management of diabetes mellitus and its complications.