Inhibitory Effect of Naturally Occurring Flavonoids on the Formation of Advanced Glycation Endproducts

Abstract

The objective of this study was to investigate the inhibitory effect of naturally occurring flavonoids on individual stage of protein glycation in vitro using the model systems of delta-Gluconolactone assay (early stage), BSA-methylglyoxal assay (middle stage), BSA-glucose assay, and G.K. peptide-ribose assay (last stage). In the early stage of protein glycation, luteolin, qucertin, and rutin exhibited significant inhibitory activity on HbA1C formation (p < 0.01), which were more effective than that of aminoguanidine (AG, 10 mM), a well-known inhibitor for advanced glycation endproducts (AGEs). For the middle stage, luteolin and rutin developed more significant inhibitory effect on methylglyoxal-medicated protein modification, and the IC50's were 66.1 and 71.8 microM, respectively. In the last stage of glycation, luteolin was found to be potent inhibitors of both the AGEs formation and the subsequent cross-linking of proteins. In addition, phenyl-tert-butyl-nitron served as a spin-trapping agent, and electron spin resonance (ESR) was used to explore the possible mechanism of the inhibitory effect of flavonoids on glycation. The results indicated that protein glycation was accompanied by oxidative reactions, as the ESR spectra showed a clear-cut radical signal. Statistical analysis showed that inhibitory capability of flavonoids against protein glycation was remarkably related to the scavenging free radicals derived from glycoxidation process (r = 0.79, p < 0.01). Consequently, the inhibitory mechanism of flavonoids against glycation was, at least partly, due to their antioxidant properties.

Olive Leaf Extracts Are a Natural Source of Advanced Glycation End Product Inhibitors

“…17 Previous structure-activity studies have shown that luteolin, among 10 other flavonoids, was the most potent inhibitor on each stage of protein glycation; flavones exhibit stronger inhibitory effects when compared with flavonols, flavanones, and isoflavones. 3 In our study, luteolin-7-O-b-D-glucopyranoside despite having a catechol group is not such an efficient inhibitor as luteolin-4 0 -O-b-D-glucopyranoside (not having vicinal hydroxyl groups). This confirms a previous study showing that glycosylation of the hydroxyl group at the C-7 position, and methylation or glycosylation of the 4 0 -hydroxyl group of flavonoids reduces anti-glycation activity.…”

“…2 Inhibition of AGE formation via blocking sugar attachment to proteins, trapping/scavenging the reactive intermediates, or breakdown of established AGE-induced cross-links constitutes an attractive therapeutic/preventive target. 1,3 Clinical trials to test the effectiveness of synthetic inhibitors are under way, although the first trials showed serious side effects. 4 Several in vitro and in vivo studies have illustrated that natural products, especially those belonging to the polyphenol family, are promising agents for the prevention of AGE formation; their inherent antioxidant capacity reinforce their potential for effective anti-glycation.…”

Effect of Moringa oleifera on advanced glycation end-product formation and lipid metabolism gene expression in HepG2 cells

“…M. oleifera leaves were found to possess hypolipidemic and antiatherosclerotic activities, and have therapeutic potential for the prevention of cardiovascular diseases (Chumark et al, 2008). The inhibitory mechanism of flavonoids against glycation may be due to their antioxidant properties (Wu and Yen, 2005). A reduction of more than 50% AGE intake could reduce approximately 30% of the circulating AGE within 1 month (Peppa et al, 2003).…”

Substituted benzenediol Schiff bases as promising new anti-glycation agents

“…Previous studies conducted on diabetic rats, demonstrated that rutin protected against the formation of skin-collagen fluorescence and also inhibited early glycation product formation [12]. Rutin also exhibited a significant inhibitory effect on glycation of haemoglobin and it was found to be more effective than aminoguanidine [13]. The percentage inhibition was calculated as follows (Equation 1):…”