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University of the Western Cape (2014)

Evaluation of the antioxidant and anti-diabesity potential of cyclopia maculata using in vitro non-cell based screening models

Matrose, Albertina Neliswa

Titre : Evaluation of the antioxidant and anti-diabesity potential of cyclopia maculata using in vitro non-cell based screening models

Auteur : Matrose, Albertina Neliswa

Université de soutenance : University of the Western Cape

Grade : Magister Scientiae - MSc (Herbal Science and Medicine) 2014

Résumé
The simultaneous increase in obesity and type 2 diabetes has resulted in a new term, ‘diabesity’, to describe individuals suffering from both diseases. Adverse effects associated with the use of the anti-obesity drug, OrlistatTM, and the anti-diabetic drug, AcarboseTM, both enzyme inhibitors, necessitate the search for alternative anti-diabesity therapeutics with less or no side effects. Furthermore, oxidative stress plays a major role in the pathogenesis of these diseases. The aim of this study was therefore to evaluate the antioxidant and anti-diabesity potential of a hot water extract of C. maculata in non-cell based assays and correlate the activities with phenolic composition. Total antioxidant capacity (TAC) was assessed in terms of free radical scavenging and iron reducing ability. The DPPH, ABTS, ORAC and FRAP assays were employed. Anti-diabesity potential was assessed in terms of the inhibition of the digestive enzymes, α-glucosidase and pancreatic lipase. The effect of fermentation was also determined by analyzing aqueous extracts of unfermented C. maculata plant material (n = 9) and their fermented counterparts (n =9). Extraction simulated the industrial scale process used for preparation of food-grade extracts. Total polyphenol content of C. maculata extracts was measured in gallic acid equivalence (GAE) and the unfermented batch of extracts contained an average of 24 g GAE/100 g. This was significantly higher than that of the fermented batch of extracts (16 g GAE/100 g). HPLC analysis showed highest quantities for mangiferin and isomangiferin. Other compounds in relatively high concentrations were iriflophenone-3 C-β-D-glucoside, hesperidin and eriocitrin. The compounds differed in the extent of degradation upon fermentation. Most affected were mangiferin and iriflophenone-3-C-β D-glucoside, i.e. 70 % decrease compared to ≤ 40 % for the other compounds. Different TAC values were obtained with different assays used, as expected due to different mechanisms and rate of reaction, with the highest TAC value obtained for the ORAC assay in the relative order TACORAC>TACABTS >TACDPPH>TACFRAP, irrespective of state of fermentation. Fermentation decreased TAC values obtained in all assays. The individual polyphenol compound content correlated significantly (P < 0.0001) with the TAC of extracts, however, the flavanone glycoside hesperidin showed no detectable antioxidant activity in the on-line HPLC antioxidant assays. A positive inhibitory activity was obtained against α-glucosidase. The extracts however, were more effective against mammalian α-glucosidase than yeast α-glucosidase. In the respective assays the extracts were, however, significantly weaker α-glucosidase inhibitors than Acarbose™ and (+)-catechin. Fermentation also decreased the activity of α-glucosidase. The lipase inhibitory activity of the extracts was compared with Orlistat™. This drug proved to be highly effective while the C. maculata extracts only showed weak inhibition of the enzyme. Once again the extracts of unfermented plant material were more effective than their fermented counterparts Based on multiple biological activities of the phenolic compounds in C. maculata, this plant might be a useful source of compounds that could provide a lead structure for the development of multiple target-oriented therapeutic modalities for the treatment of diabesity. The major compounds in C. maculata extracts, i.e. mangiferin, isomangiferin and iriflophenone-3-C-β-D-glucoside, could be used as chemical markers to obtain a standardized antioxidant nutraceutical. The anti-diabesity activity of these compounds, however, needs further exploration before they can be used as bioactive markers for a nutraceutical product aimed at the anti-diabesity market.

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