Antidiabetic activity of lipophilic (-)-epigallocatechin-3-gallate derivative under its role of alpha-glucosidase inhibition.
(-)-Epigallocatechin-3-gallate (EGCG), a component of catechins, has been shown to reduce blood glucose levels. In the present study, we investigated the antidiabetic activity and its mechanism of lipophilic EGCG derivative (L-EGCGd) in streptozotocin (STZ)-induced diabetic rats. L-EGCGd was chemically modified from traditional hydrophilic EGCG. After 30 days treatment, plasma levels of glucose were significantly reduced by 40.5+/-7.0% and 17.0+/-2.8% in groups administered 50 or 25 mg kg(-1)d(-1) L-EGCGd, respectively, as compared with that in the diabetic control group. Lipid metabolites, such as total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDLC) were effectively attenuated by L-EGCGd administration, but plasma HDLC levels did not change significantly. The oral glucose tolerance test (OGTT) greatly revealed the improved ability of glucose tolerance with treatment of L-EGCGd. L-EGCGd only retarded the postprandial rise in blood glucose with sucrose loading but not glucose loading. And activity of alpha-glucosidase was inhibited by 50% at the concentration of 246.6 microg ml(-1) L-EGCGd. As a result, we first demonstrated that the purified form of compound L-EGCGd possessed the hypoglycemic effect under its role of alpha-glucosidase inhibition, and therefore should be possibly accepted as an alternative oral medication protecting patients against postprandial hyperglycemic toxicity on the treatment of diabetes and its complications.
Li
Ting
T
School of Pharmacy, East China University of Science and Technology, Mailbox 268, 130 Meilong Road, Shanghai 200237, P.R. China.
Liu
Jianwen
J
Zhang
Xiaodong
X
Ji
Guang
G
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001835:Body Weight; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D008055:Lipids; D002392:Catechin; C045651:epigallocatechin gallate