α-GLUCOSIDASE INHIBITORS FROM EDIBLE PLANTS

Abstract

The present study investigated α-glucosidase inhibitors with the aim of developing therapeutics for the treatment of type 2 diabetes mellitus. We examined the inhibitory effect of edible plants against α-glucosidase. The leaves of Piper sarmentosum Roxb, seed pulp of Sesamum indicum L. and aerial part of Orthosiphon aristatus (Blume) Miq were selected for this investigation. Bioassay-guided fractionation led to the isolation of active compounds. The dichloromethane and methaol extracts from leaves of P. sarmentosum afford three new phenylpropanoyl amides, named chaplypupyrrolidones A (1) and B (2) and deacetylsarmentamide B (7),along with six known named N-(3-(4′methoxyphenyl)propanoyl)pyrrole (3), N-(3-phenylpropa-noyl)pyrrole (4), asaricin (5) and cinnamic acid (6), kaemferol-3-O-rhamnoside (8) and dihydrokaempferol-3-O-glucoside (9). Of isolated compounds, 2 showed most potent inhibition against yeast α-glucosidase with IC50 value of 430±1.2 µM. Kinetic evaluation of 2 suggested that it acts as a noncompetitive inhibitor. The methanol crude extract from seed pulp of Sesamum indicum L. afforded various three lignans named sesamin (10), sesamolin (11) and sesaminol monoglucoside (12). Of the compounds isolated, sesamin (10), the major component revealed inhibitory activity against yeast α-glucosidase with IC50 value of 450±1.9 µM. The kinetic study indicated that 10 showed competitive manner. The dichloromethane extract of aerial part of Orthosiphon aristatus (Blume) Miq was investigated using an α-glucosidase-guided isolation. Four flavonoids named sinensetin (13), salvigenin (14), tetramethylscutellarein (15) and 3,7,4'-tri-O-methylkaempferol (16) together with a diterpenoid named orthosiphol A (17) were isolated. Flavonoids 15 and 16 inhibited yeast α-glucosidase with IC50 values of 6.34 and 0.75 mM, respectively, whereas orthosiphol A (17) selectively inhibited maltase with an IC50 value of 6.54 mM. A kinetic investigation of 5 indicated that it retarded maltase function in a noncompetitive manner. In addition to edible plants, we also investigated α-glucosidase inhibition, antioxidant and LPS-elicited induction of various berry-defatted soybean flour (DSF) conmplexes. Blueberry-DSF complex (BB-DSF) and blackcurrant-DSF complex (BLC-DSF) were rich in anthocyanins (ANC), and proanthocyanidins (PAC). All polyphenol-enriched DSF exhibited significant against rat α-glucosidase (maltase and sucrase). BB-DSF was the most potent rat α-glucosidase inhibitor with IC50 values of 2.46 for maltase and 0.90 mg/mL for sucrase respectively. The mechanism underling inhibition against maltase was proved to be mixed-type manner while sucrase inhibited by noncompetitive manner. All polyphenol-enrich DSF demonstrated higher level of phenolic components, antioxidant capacity (DPPH) and exhibited LPS-elicited induction in RAW 264.7 cells. The data suggested that polyphenol-enriched DSF can provide a high-protein, low-sugar ingredient for novel food and dietary supplements.