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.
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 alpha-(1,6)-glycosidic linkage. It was found that Acv-simmondsin was a potent competitive inhibitor of alpha-glucosidase with the Ki value of 0.69 microM and a mixed type inhibitor of alpha-amylase with the Ki and KI of 20.78 microM and 26.31 microM, 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.
National Laboratory for Functional Food Carbohydrates, and Department of Food Science and Technology, School of Agricultural Biotechnology, Seoul National University, Suwon 441-744, Korea.
Jin-Sook
JS
Baek
Hye-Young
HY
Kim
Thomas P
TP
Abbott
Tae-Wha
TW
Moon
Soo-Bok
SB
Lee
Cheon-Seok
CS
Park
Kwan-Hwa
KH
Park
D000097:Acetonitriles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000606:Amino Sugars / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001835:Body Weight; D002240:Carbohydrate Sequence; D003510:Cyclohexanes; D004435:Eating / Q000187:drug effects*; D005947:Glucose / Q000031:analogs & derivatives; D005960:Glucosides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006031:Glycosylation; D006868:Hydrolysis; D006943:Hyperglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008969:Molecular Sequence Data; D019518:Postprandial Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013824:Thermus / Q000201:enzymology*; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
D000097:Acetonitriles; D000606:Amino Sugars; D019440:Anti-Obesity Agents; D001786:Blood Glucose; D003510:Cyclohexanes; D005960:Glucosides; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; C076099:acarviosine; D006026:Glycoside Hydrolases; D000516:alpha-Amylases; D005947:Glucose; C089377:simmondsin