Exposure to polyphenol-enriched rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) extracts : implications of metabolism for the oxidative status in rat liver

[摘要] ENGLISH ABSTRACT: Potential beneficial and/or adverse modulatory effects of polyphenol-enriched extracts ofrooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) on the antioxidant homeostasis inthe liver were investigated. Phase II metabolism of aspalathin and mangiferin, the majorpolyphenols of rooibos and honeybush respectively, was assessed for potential glucuronidationand sulphation. Glucuronidation resulted in a loss of antioxidant activity for aspalathin andmangiferin in post-column HPLC-DAD-DPPH• and HPLC-DAD-ABTS•+ assays and also adecreased activity of iron chelating properties of mangiferin in the FRAP assay. Twoindependent studies for 28 and 90 days with polyphenol-enriched extracts (PEEs) ofunfermented rooibos [Aspalathus linearis (PER)] and honeybush [Cyclopia. subternata(PECsub) and C. genistoides (PECgen)] in male Fischer rats were conducted to assesspossible beneficial and/or adverse biological effects. PECgen was only included in the 28 daystudy. PEEs were characterised by in vitro antioxidant assays and HPLC analysis. Theimportance of detailed chemical characterization of rooibos and honeybush when investigatingbiological effects in vivo is clear as distinctive biological effects and major differences incompositions were evident. Biological parameters included were serum chemical parameters,activities of selected antioxidant enzymes, levels of glutathione and the modulation ofexpression of oxidative stress and antioxidant defense related genes in the liver. Sub-chronic(90 days) exposure of rats to PER and PECsub both adversely affected iron absorptionsignificantly (P<0.05) and significantly (P<0.05) and markedly lowered levels of reducedglutathione (GSH) in the liver. The high levels of polyphenol intake were implicated andinteraction with glutathione was postulated to occur via catechol o-quinone conjugations withGSH. This was also implicated in the significantly (P<0.05) increased activity of glutathionereductase (GR) following 28 days. These findings suggest that PEEs from rooibos andhoneybush have the potential to alter the glutathione homeostasis, which could contribute tooxidative status in the liver. PECsub resulted in alterations in the liver biliary system which wasmanifested as significantly (P<0.05) increased serum total bilirubin (Tbili) and alkalinephosphatase (ALP), depending on the age of the rats, level of total polyphenols and duration ofexposure. The expression of a number of oxidative stress and antioxidant defense relatedgenes were differentially altered by the PEEs of rooibos and honeybush in rat liver and furtherindicated potential oxidative stress. Modulatory effects of PEEs on expression of 84 of thesegenes in rat liver were assessed with a quantitative real-time reverse transcription polymerasechain reaction (RT-PCR) array and provided additional insights into the possible adverse andprotective effects of rooibos and honeybush. Further investigation on total polyphenol doselevels and time of exposure in the application of PEEs of rooibos and honeybush as dietary supplements and functional foods is recommended and will also be of value in anticipatedregulatory requirements for future substantiation of safety and efficacy.

[发布机构] Stellenbosch University