Differential Modulation of Gene Expression Encoding Hepatic and Renal Xenobiotic Metabolizing Enzymes by an Aspalathin-Enriched Rooibos Extract and Aspalathin

Sameega Abrahams; Sedicka Samodien; Mariska Lilly; Elizabeth Joubert; Wentzel Gelderblom

doi:10.1055/a-0656-7500

Planta Medica, Table of Contents

Planta Med 2019; 85(01): 6-13
DOI: 10.1055/a-0656-7500

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Differential Modulation of Gene Expression Encoding Hepatic and Renal Xenobiotic Metabolizing Enzymes by an Aspalathin-Enriched Rooibos Extract and Aspalathin

Sameega Abrahams

¹Research part of the MSc degree of Mrs Abrahams MSc dissertation obtained from the Department of Medical Biosciences, University of Western Cape, South Africa

,

Sedicka Samodien

²Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, Bellville, South Africa

,

Mariska Lilly

²Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, Bellville, South Africa

,

Elizabeth Joubert

³Plant Bioactives Group, Agricultural Research Council, Infruitec-Nietvoorbij, Stellenbosch, South Africa

⁴Department of Food Science, Stellenbosch University, Stellenbosch, South Africa

,

Wentzel Gelderblom

²Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, Bellville, South Africa

⁵Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa

› Author Affiliations

Abstract

Modulation of the expression of hepatic and renal genes encoding xenobiotic metabolizing enzymes by an aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was investigated in the liver and kidneys of F344 rats following dietary exposure of 28 d, as well as selected xenobiotic metabolizing genes in rat primary hepatocytes. In the liver, GRE upregulated genes (p < 0.05) encoding aldehyde dehydrogenase, glucose phosphate isomerase, and cytochrome P450 while 17β-hydroxysteroid dehydrogenase 2 (Hsd17β2) was downregulated. In primary hepatocytes, GRE lacked any effect, while aspalathin downregulated Hsd17β2, mimicking the effect of GRE in vivo, and upregulated catechol-O-methyl transferase and marginally (p < 0.1) cytochrome P450 2e1. In the kidneys, GRE upregulated (p < 0.05) genes encoding the phase II xenobiotic metabolism enzymes, glutathione-S-transferase mµ and microsomal glutathione-S-transferase, while downregulating genes encoding the ATP binding cassette transporter, cytochrome P450, gamma glutamyltransferase 1, and N-acetyltransferase 1. Differential modulation of the expression of xenobiotic metabolizing genes in vivo and in vitro by GRE is dose-related, duration of exposure, the tissue type, and interactions between specific polyphenol and/or combinations thereof. Aspalathin is likely to be responsible for the downregulation of estradiol and testosterone catabolism by GRE in the liver. The differential gene expression by GRE in the liver and kidneys could, depending on the duration exposure and dose utilized, determine the safe use of such an extract in humans for specific health and/or disease outcomes.

Key words

Leguminosae - Aspalathus linearis - xenobiotic metabolizing enzymes - hepatocytes, qRT-PCR

Full Text

References

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