Extracts of bixa inhibit glycation and AGEs formation in vitro

Accelerated formation of advanced glycation an end-products (AGEs) has been complicated in the pathogenesis of various diabetic complications. Several natural and synthetic compounds have been proposed and tested, as inhibitors of glycation and AGEs formation. The present study reports effect of seed extracts of. B. orellana on inhibition of glycation and AGEs formation in vitro. We have identified five known active principles namely geranylgeranyl (1), farnesylacetone (2), geranylgeranyl octadecanoato (3), geranylgeranyl formiate (4) and geranylgeranyl acetate (5) from chloroform extract of the seeds. We measured the effect of various concentrations of active principles (1 to 5) on the glycemic status of diabetic STZ Wistar strain albino rats. Among the various concentrations tested, only the geranylgeranyl octadecanoato showed hypoglycemic activity, may be due to stimulating peripheral utilization of glucose, improving glucose uptake by adipose tissue and muscle. In contrast, rats treated with geranylgeranyl acetate showed hyperglycemia by decreasing the levels of plasma insulin levels. In vitro assays were also performed to determine positive mechanisms of active principles of seed extracts in inhibiting glycation and AGEs formation. Geranylgeranyl octadecanoate was found to be the most active principle affecting inhibition of AGEs followed by geranylgeraniol >farnesilacetona, geranylgeranyl formiate> geranylgeranyl acetate. The mechanim of inhi bition on AGEs of geranylgeraniol derivatives occurs in the stage of the formation of fructosamine (Amadori compounds). These mechanisms may help to provide a protective effect against hyperglycemiamediated protein damage. These observations provide investigators additional therapeutic options for treatment of various complications of diabetes.