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Inhibition of aldose reductase by Gentiana lutea extracts.

ABSTRACT: Accumulation of intracellular sorbitol due to increased aldose reductase (ALR2) activity has been implicated in the development of various secondary complications of diabetes. Thus, ALR2 inhibition could be an effective strategy in the prevention or delay of certain diabetic complications. Gentiana lutea grows naturally in the central and southern areas of Europe. Its roots are commonly consumed as a beverage in some European countries and are also known to have medicinal properties. The water, ethanol, methanol, and ether extracts of the roots of G. lutea were subjected to in vitro bioassay to evaluate their inhibitory activity on the ALR2. While the ether and methanol extracts showed greater inhibitory activities against both rat lens and human ALR2, the water and ethanol extracts showed moderate inhibitory activities. Moreover, the ether and methanol extracts of G. lutea roots significantly and dose-dependently inhibited sorbitol accumulation in human erythrocytes under high glucose conditions. Molecular docking studies with the constituents commonly present in the roots of G. lutea indicate that a secoiridoid glycoside, amarogentin, may be a potential inhibitor of ALR2. This is the first paper that shows G. lutea extracts exhibit inhibitory activity towards ALR2 and these results suggest that Gentiana or its constituents might be useful to prevent or treat diabetic complications.

SUBMITTER: Akileshwari C

PROVIDER: S-EPMC3403369 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Inhibition of aldose reductase by Gentiana lutea extracts.

Akileshwari Chandrasekhar C Muthenna Puppala P Nastasijević Branislav B Joksić Gordana G Petrash J Mark JM Reddy Geereddy Bhanuprakash GB

Experimental diabetes research 20120715

Accumulation of intracellular sorbitol due to increased aldose reductase (ALR2) activity has been implicated in the development of various secondary complications of diabetes. Thus, ALR2 inhibition could be an effective strategy in the prevention or delay of certain diabetic complications. Gentiana lutea grows naturally in the central and southern areas of Europe. Its roots are commonly consumed as a beverage in some European countries and are also known to have medicinal properties. The water, ...[more]

PMID: 22844269

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Project description:Diabetes mellitus is a chronic disease that is becoming a serious global health problem. Diabetes has been considered to be one of the major risks of cataract and retinopathy. Synthetic and natural product inhibitors of carbohydrate degrading enzymes are able to reduce type 2 diabetes and its complications. For a long time, potatoes have been portrayed as unhealthy for diabetic patients by some nutritionist due to their high starch content. However, purple and red potato cultivars have received considerable attention from consumers because they have high levels of polyphenolic compounds that have potent antioxidant activities. In this study, we screened the total phenolics (TP) and total anthocyanins (TA) and analyzed the phenolic and anthocyanin compounds in selected potato cultivars and advanced selections with distinct flesh colors (purple, red, yellow and white). Purple and red potato cultivars had higher levels of TP and TA than tubers with other flesh colors. Chlorogenic acid is the predominant phenolic acid, and major anthocyanin is composed of the derivatives of petunidin, peonidin, malvidin and pelargonidin. We tested the potential inhibitory effect of potato extracts on the activities of ?-amylase and ?-glucosidase, which were targeted to develop antidiabetic therapeutic agents. We also measured inhibitory effect of potato extracts on aldose reductase (AR) which is a key enzyme that has been a major drug target for the development of therapies to treat diabetic complications. Purple flesh tubers extract showed the most effective inhibition of ?-amylase, ?-glucosidase, and aldose reductase with IC50 values 25, 42, and 32 ?g/ml, respectively. Kinetic studies showed that anthocyanins are noncompetitive inhibitors of these enzymes, whereas phenolic acids behaved as mixed inhibitors for ?-amylase and ?-glucosidase and noncompetitive inhibitors for AR. This study supports the development of a positive and healthful image of potatoes, which is an important issue for consumers.

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Inhibition of aldose reductase by Gentiana lutea extracts.

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Inhibition of aldose reductase by Gentiana lutea extracts.

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