α-Glucosidase inhibition and antihyperglycemic activity of prenylated xanthones from Garcinia mangostana

• Published in: Phytochemistry (Oxford) 2011-12, Vol.72 (17), p.2148-2154
• Main Authors: Ryu, Hyung Won, Cho, Jung Keun, Curtis-Long, Marcus J., Yuk, Heung Joo, Kim, Young Soo, Jung, Sunin, Kim, Young Suk, Lee, Byong Won, Park, Ki Hun
• Format: Article
• Language: English
• Subjects: 1-Deoxynojirimycin - pharmacology; Animals; Antihyperglycemic; Biological and medical sciences; Blood Glucose - metabolism; Chemical constitution; Disease Models, Animal; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Enzyme kinetic; Fruit; Fundamental and applied biological sciences. Psychology; Garcinia mangostana; Garcinia mangostana - chemistry; Glycoside Hydrolase Inhibitors; Guttiferae; Hyperglycemia - blood; Hyperglycemia - chemically induced; Hyperglycemia - drug therapy; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Inhibitory Concentration 50; Male; Maltose - metabolism; Phytotherapy; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant physiology and development; Postprandial Period; Rats; Rats, Sprague-Dawley; Seeds; Xanthones - isolation & purification; Xanthones - pharmacology; Xanthones - therapeutic use; α-Glucosidase inhibitor
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2011.08.007

A series of isolated xanthones from mangosteen showed potent α-glucosidase inhibitory properties, and one isolated xanthone has a very rare 2-oxoethyl group C-8. The crude mangosteen extract exhibited a significant reduction of blood glucose levels in STZ-induced rats. [Display omitted] . ► The potent α-glucosidase inhibitors 1– 16 were isolated from Mangosteen. ► An isolated xanthone has a very rare 2-oxoethyl group on C-8. ► The crude extract exhibited a significant glucose reduction in STZ-induced rats. An ethanol extract of the fruit case of Garcinia mangostan, whose most abundant chemical species are xanthones, showed potent α-glucosidase inhibitory activity (IC 50 = 3.2 μg/ml). A series of isolated xanthones ( 1– 16) demonstrated modest to high inhibition of α-glucosidase with IC 50 values of 1.5–63.5 μM. In particular, one hitherto unknown xanthone 16 has a very rare 2-oxoethyl group on C-8. Kinetic enzymatic assays with a p-nitrophenyl glucopyranoside indicated that one of them, compound ( 9) exhibited the highest activity ( K i = 1.4 μM) and mixed inhibition. Using, a physiologically relevant substrate, maltose, as substrate, many compounds ( 6, 9, 14, and 15) also showed potent inhibition which ranged between 17.5 and 53.5 μM and thus compared favorably with deoxynojirimycin (IC 50 = 68.8 μM). Finally, the actual pharmacological potential of the ethanol extract was demonstrated by showing that it could elicit reduction of postprandial blood glucose levels. Furthermore, the most active α-glucosidase inhibitors ( 6, 9, and 14) were proven to be present in high quantities in the native seedcase by a HPLC chromatogram.