Isolation And Characterization Of Natural Alpha-Glucosidase Inhibitors From Antioxidant Rich Red Wine Grapes (vitis Vinifera)

<p> <strong>Background:</strong> Diabetes is currently a global public health problem affecting people at all ages. Dietary antioxidants have been associated with a reduced risk of type 2 diabetes. Grape pomace contains considerable amounts of polyphenols and it has been reported to exhibit an inhibitory activity against alpha- glucosidases. Alpha-glucosidases, in turn, play a major role in controlling starch digestion and therefore postprandial blood glucose, a target for diabetes management. </p> <p> <strong>Objective:</strong> This study aims to investigate the anti-diabetes potential of a selection of six grape pomaces and prepare and purify active components in the active variety that specifically inhibit intestinal alpha-glucosidases. The study was also designed to evaluate the applicability of the isolated active components as natural inhibitors of alpha-glucosidases. </p> <p> <strong>Methods:</strong> Chambourcin, Merlot, Norton, Petit Verdot, Syrah and Tinta Cao red wine grape pomace extracts were assessed for their rat intestinal alpha-glucosidase inhibiting activity and antioxidant properties via biochemical assays and UV detection. Then, the grape pomace variety shown to potently inhibit the enzyme was subjected to bioactivity-guided fractionation and the isolated active component was identified via analytical chemistry techniques. The characterized compound was then tested for functional food applicability via stability, enzyme specificity and cytotoxicity testing. </p> <p> <strong>Results:</strong> Tinta Cao grape pomace extract was the most potent alpha-glucosidase inhibiting variety and possessed a remarkable antioxidant activity, both properties of which appeared to be correlated. HPLC analysis did not yield an antioxidant responsible for the observed trend. Hence, bioactivity-guided fractionation of the extract was pursued, yielding a pure active compound that was determined to be D-Glucopyranose 6-{(2E)-3-(4-Hydroxyphenyl)prop-2-enoate}, which also exhibited a strong antioxidant activity. Further testing indicated that the compound inhibits alpha-glucosidase and not alpha-amylase, and specifically inhibits the maltase and isomaltase moieties of alpha-glucosidase, in a dose-dependent fashion. The compound was fairly stable under different environmental and storage conditions, and it was also not cytotoxic to animal cells.</p> <p> <strong>Conclusion:</strong> Red grape pomace, namely Tinta Cao, is a promising bioresource for the future development of a food-derived antidiabetic agent. At least one component, D-Glucopyranose 6-{(2E)-3-(4-Hydroxyphenyl)prop-2-enoate}, isolated from Tinta Cao grape pomace appears to potently and specifically inhibit mammalian intestinal alpha-glucosidases while exhibiting a notable ability to quench free radicals. It may thus represent an alternative future strategy for diabetes management and a novel antioxidant compound. Pre-clinical and clinical testing will validate the obtained results in vivo.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Nutrition and Food Science

Year dc:date.available

2014

Author dc:creator

• Kadouh, Hoda Chaouki

Contributors dc:contributor

• Kequan (Kevin) Zhou

• Alpha-Glucosidases
• Antioxidant
• Diabetes
• Grape Pomace
• Tinta Cao
• Alternative and Complementary Medicine
• Nutrition
• Pharmacology

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/889

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-1888