Department of Food Science

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Browsing Department of Food Science by Subject "Alpha-glucosidase -- Inhibitors"

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    Development of a gastroretentive anti-diabetic nutraceutical incorporating polyphenol-enriched fractions of Cyclopia genistoides
    (Stellenbosch : Stellenbosch University, 2020-04) Miller, Neil; Joubert, Elizabeth; Manley, Marena; Malherbe, Christiaan Johannes; Stellenbosch University. Faculty of AgriSciences. Dept. of Food Science.
    ENGLISH ABSTRACT: Extracts of honeybush (Cyclopia genistoides) containing glycosylated xanthones, mangiferin (1) and isomangiferin (2), and benzophenones, 3-β-D-glucopyranosyliriflophenone (3) and 3-β-D-glucopyranosyl-4- O-β-D-glucopyranosyliriflophenone (4) inhibit α-glucosidase (AG), a key digestive enzyme and treatment target for postprandial hyperglycaemia associated with type 2 diabetes. Ultrafiltered green C. genistoides extract served as the starting material for the development of an optimised production protocol for xanthone- and benzophenone-enriched fractions (XEFs and BEFs) by macroporous adsorbent resin chromatography. Inter-batch variation in the phenolic content of the raw material manifested as variation in the composition and degree of enrichment of target compounds in XEFs and BEFs. The in vitro AG inhibitory effects of C. genistoides phenolics, extract, XEF and BEF, combined with the commercial AG inhibitor (AGI), acarbose, were investigated using the combination index. The single-compound AGIs demonstrated potency in the descending order: acarbose (IC50 = 44.3 µM) > 1 (102.2 µM) > 2 (119.8 µM) > 3 (237.5 µM) > 4 (299.4 µM). Potency of the extract and fractions was strongly linked to their xanthone content. XEFs (xanthone content = 22.3–48.1 g/100 g) were produced using ten different batches of plant material and tested at a fixed concentration (160 µg/mL), achieving 63 to 72% enzyme inhibition. BEFs (benzophenone content = 11.4– 21.7 g/100 g) achieved enzyme inhibition of 26 to 34%. There was a weak linear correlation (R² < 0.43) between the target compound content of the fractions and their AG inhibition potency. Synergistic AG inhibition at > 50% effect levels was observed for all combinations of acarbose with fractions (XEFs, BEFs) or target compounds (1–4). Combinations of acarbose with 1 and 2 gave the highest theoretical in vitro acarbose dose reduction (> six-fold) across all effect levels. XEFs showed greater theoretical acarbose dose reduction (≈ four-fold at 50% inhibition) than BEFs, demonstrating the potential of XEFs as a supplement to acarbose. In a subsequent in vivo oral sucrose tolerance test in normal and diabetic Wistar rats, XEF (single orally administered dose of 300 mg/kg body weight) did not result in significantly lowered postprandial blood glucose or in an improved effect in combination with acarbose (5 mg/kg body weight). The suitability of C. genistoides phenolics as non-toxic active pharmaceutical ingredients (APIs) was confirmed in a liver cell model, which indicated no cytotoxicity following acute or chronic exposure. Ex vivo intestinal transport studies using porcine jejenum showed that the target compounds (1–4) are poorly absorbed, confirming their suitability as APIs aimed at an intestinal target, and re-emphasising the low risk of systemic toxicity. XEF and BEF were subsequently incorporated (alone and combined) in a non-effervescent gastroretentive tablet formulation containing low-density styrene-divinylbenzene co-polymer as floating agent. The tablets floated in an in vitro medium (0.1 N HCl) for at least 8 h and released APIs through a diffusion-based process, described by the Weibull model (R² > 0.99). API degradation during storage under adverse conditions (12 weeks at 40 °C) followed first order reaction kinetics with the order of compound stability: 4 > 1 > 2 > 3.