In vitro α-glucosidase inhibition by honeybush (Cyclopia genistoides) food ingredient extract — potential for dose reduction of acarbose through synergism

Extracts of Cyclopia species are used as food ingredients. In vitro α-glucosidase (AG) inhibition by ultrafiltered C. genistoides extract, fractions enriched in xanthones (XEF) and benzophenones (BEF), as well as mangiferin, isomangiferin, 3-β-D-glucopyranosyl-iriflophenone (I3G) and 3-β-D-glucopyranosyl-4-O-β-D-glucopyranosyliriflophenone (IDG) was determined with acarbose as positive control. XEF was more potent than the extract and BEF (IC50 = 43.3, 95.5 and 205.7 μg mL−1, respectively). Compounds demonstrated potency in descending order: acarbose (IC50 = 44.3 μM) > mangiferin (102.2 μM) > isomangiferin (119.8 μM) > I3G (237.5 μM) > IDG (299.4 μM). The combination index (CI) was used to determine synergism (CI six-fold) across all effect levels were calculated for combinations of acarbose with mangiferin or isomangiferin, explaining the greater acarbose dose reduction potential of XEF vs BEF. The effect of batch-to-batch variation (n = 10) of the raw plant material on AG inhibition was quantified at a fixed concentration (160 μg mL−1). XEFs (xanthone content = 223–481 g kg−1) achieved AG inhibition of 63–72%, whereas BEFs (benzophenone content = 114–251 g kg−1) achieved AG inhibition of 26–34%, with weak linear correlation (R2 < 0.43) between target compound content of the fractions and their achieved AG inhibition. These results emphasise the challenge to achieve consistent activity and thus also dose reduction when using complex mixtures of plant origin.