Acarviosine-simmondsin, a Novel Compound Obtained from Acarviosine-glucose and Simmondsin by Thermus Maltogenic Amylase and Its in vivo Effect on Food Intake and Hyperglycemia

Abstract

  Simmondsin was modified with acarviosine-glucose using the transglycosylation activity of Thermus maltogenic amylase to synthesize a novel compound with both antiobesity and hypoglycemic activity. The LC/MS and ¹³C NMR analyses confirmed that the structure of the major transglycosylation product was acarviosine-simmondsin (Acv-simmondsin), in which acarviosine was attached to the glucose moiety of simmondsin by an α-(1,6)-glycosidic linkage. It was found that Acv-simmondsin was a potent competitive inhibitor of α-glucosidase with the K_i value of 0.69 μM and a mixed type inhibitor of α-amylase with the K_i and K_I of 20.78 μM and 26.31 μM, respectively. The administration of Acv-simmondsin (0.1 g/100 g diet/day) to mice for 5 days significantly reduced food intake by 35%, compared to 25% with simmondsin in control obese mice. Acv-simmondsin (50 mg/kg BW) suppressed the postprandial blood glucose response to sucrose (1 g/kg BW) by 74%, compared to 71% with acarbose, in normal rats.