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Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents.


Although the pathogenic features of reduced amylase secretion and the underlying mechanisms linking islets and acinar cells have been extensively examined in animal and cellular studies [14–19], clinical evidence supporting such exocrine-endocrine relationships has not been established in large human studies. Inhibition of Angiotensin I-Converting Enzyme (ACE) is also considered useful as a therapeutic approach in the treatment of high blood pressure, one of the long-term complications of diabetes. In vivo, the findings indicated that soy isoflavones stimulated insulin secretion, increased the hepatic glycogen content and suppressed blood glucose level. Meanwhile, the pattern of changes in plasma glucose levels during the OGTTs suggest that subjects with low serum amylase have lower glucose tolerance. Plants used in the study along with the parts used and their hypoglycemic properties are listed in Table 1 while their voucher numbers are listed as an additional file 1 . Results of the study showed that median lipase concentration was increased throughout the study period. The rationale for performing extractions from polar to non-polar solvents is to confirm and validate the inhibitory activity in the aqueous extractions performed in the traditional manner as well as to search for newer, more potent inhibitory compounds in the organic solvents.

One goal of therapy for diabetic patients, especially non-insulin-dependent diabetes mellitus (type 2 diabetes), is the maintenance of normal blood glucose levels after a meal (postprandial hyperglycemia) (3, 6). Fluorescence and CD confirmed the involvement of tryptophan and tyrosine in ligand binding to HPA. Correlation of the reduction in serum amylase and lipase levels with the duration of disease revealed a remarkable decrease in both enzymes in patients with long-standing disease (76% and 39%) in type 1 diabetic patients. Thus, the limonoids azadiradione and gedunin could bind and inactivate HPA (anti-diabetic target) and may prove to be lead drug candidates to reduce/control post-prandial hyperglycemia.

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