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Planta Med 2021; 87(04): 325-335
DOI: 10.1055/a-1265-1945
Formulation and Delivery Systems of Natural Products
Original Papers

Physicochemical Stability of Enriched Phenolic Fractions of Cyclopia genistoides and ex vivo Bi-directional Permeability of Major Xanthones and Benzophenones

Neil Miller
1   Plant Bioactives Group, Post-Harvest and Agro-processing Technologies, Agricultural Research Council (ARC) Infruitec-Nietvoorbij, Stellenbosch, South Africa
2   Department of Food Science, Stellenbosch University, Stellenbosch, South Africa
,
Christiaan Johannes Malherbe
1   Plant Bioactives Group, Post-Harvest and Agro-processing Technologies, Agricultural Research Council (ARC) Infruitec-Nietvoorbij, Stellenbosch, South Africa
,
Werner Gerber
3   Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
,
Josias H. Hamman 
3   Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
,
Marieta van der Rijst
4   Biometry Unit, Agricultural Research Council, Stellenbosch, South Africa
,
Marique Aucamp
5   School of Pharmacy, University of the Western Cape, Bellville, South Africa
,
Elizabeth Joubert 
1   Plant Bioactives Group, Post-Harvest and Agro-processing Technologies, Agricultural Research Council (ARC) Infruitec-Nietvoorbij, Stellenbosch, South Africa
2   Department of Food Science, Stellenbosch University, Stellenbosch, South Africa
› Author AffiliationsSupported by: National Research Foundation of South Africa 104908
Supported by: National Research Foundation of South Africa 106988
Supported by: National Research Foundation of South Africa 108667
Supported by: National Research Foundation of South Africa 85277
› Further Information
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Abstract

Fractions of an ultrafiltered Cyclopia genistoides extract, respectively enriched in xanthones and benzophenones, were previously shown to inhibit mammalian α-glucosidase in vitro. The present study investigated ex vivo intestinal transport of these fractions, using excised porcine jejunal tissue, to determine whether the gut could be a predominant in vivo site of action. The major bioactive compounds, the xanthones (mangiferin, isomangiferin) and benzophenones (3-β-D-glucopyranosyliriflophenone, 3-β-D-glucopyranosyl-4-O-β-D-glucopyranosyliriflophenone) exhibited poor permeation in the absorptive direction with a relatively high efflux ratio (efflux ratio > 1). The efflux ratio of 3-β-D-glucopyranosyl-4-O-β-D-glucopyranosyliriflophenone (3.05) was similar to rhodamine 123 (2.99), a known substrate of intestinal P-glycoprotein 1 efflux transporters. Low epithelial membrane transport rates, coupled with efflux mechanisms, would effectively concentrate these bioactive compounds at the target site (gut lumen). Storage stability testing and moisture sorption assays of the xanthone-enriched fraction, benzophenone-enriched fraction, and ultrafiltered Cyclopia genistoides extract were performed to determine their susceptibility to physical and chemical degradation during storage. Hygroscopicity of the powders, indicated by moisture uptake, decreased in the order: benzophenone-enriched fraction (22.7%) > ultrafiltered Cyclopia genistoides extract (14.0%) > xanthone-enriched fraction (10.7%). 3-β-D-Glucopyranosylmaclurin, a minor benzophenone, was the least stable of the compounds, degrading faster in the benzophenone-enriched fraction than in ultrafiltered Cyclopia genistoides extract, suggesting that the ultrafiltered extract matrix may provide a degree of protection against chemical degradation. Compound degradation during 12 wk of storage at 40 °C in moisture-impermeable containers was best explained by first order reaction kinetics.

Key words

Ex vivo intestinal transport - xanthones - benzophenones - Cyclopia genistoides - Fabaceae - honeybush

Supporting Information

    Supporting information can be found in the online version of this article. Included are trans-epithelial electrical resistance data for the ex vivo transport experiments; compositions of the saturated salt solutions for moisture sorption analysis; physicochemical attributes of the major compounds relevant to the Lipinski rule of 5 criteria, and a description of the quantification of D-pinitol content in the extract and fractions.

  • Supporting Information


Publication History

Received: 21 May 2020

Accepted after revision: 14 September 2020

Article published online:
03 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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