Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis) Extract Affects Rat Liver Function and Antioxidant Status.

Johanna Van Der Merwe,Dalene De Beer,Wentzel Gelderblom,Elizabeth Joubert

doi:10.3390/molecules201219868

Abstract

An aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was fed to male Fischer rats in two independent studies for 28 and 90 days. The average dietary total polyphenol (TP) intake was 75.6 and 62.7 mg Gallic acid equivalents (GAE)/kg body weight (bw)/day over 28 and 90 days, respectively, equaling human equivalent doses (HEDs) of 12.3 and 10.2 GAE mg/kg bw/day. Aspalathin intake of 29.5 mg/kg bw/day represents a HED of 4.8 mg/kg bw/day (90 day study). Consumption of GRE increased feed intake significantly (p < 0.05) compared to the control after 90 days, but no effect on body and organ weight parameters was observed. GRE significantly (p < 0.05) reduced serum total cholesterol and iron levels, whilst significantly (p < 0.05) increasing alkaline phosphatase enzyme activity after 90 days. Endogenous antioxidant enzyme activity in the liver, i.e., catalase and superoxide dismutase activity, was not adversely affected. Glutathione reductase activity significantly (p < 0.05) increased after 28 days, while glutathione (GSH) content was decreased after 90 days, suggesting an altered glutathione redox cycle. Quantitative Real Time polymerase chain reaction (PCR) analysis showed altered expression of certain antioxidant defense and oxidative stress related genes, indicative, among others, of an underlying oxidative stress related to changes in the GSH redox pathway and possible biliary dysfunction.

Highlights

Phytochemicals, such as plant polyphenols, are associated with beneficial effects in humans, but considerable scientific evidence exists to suggest that chronic consumption, when consumed at high dose levels, may lead to adverse biological effects such as altering the cellular redox status due to their pro-oxidative activity [1]
Beneficial antioxidant properties can be outweighed by adverse effects and the unregulated use of commercially available polyphenol-enriched foods or dietary supplements are of concern [2,5]
The current study provided evidence that consumption of high levels of an aspalathin-enriched rooibos extract could lead to some adverse effects in the liver, but more research is needed to determine the total polyphenol and/or aspalathin thresholds for these outcomes

Summary

Introduction

Phytochemicals, such as plant polyphenols, are associated with beneficial effects in humans, but considerable scientific evidence exists to suggest that chronic consumption, when consumed at high dose levels, may lead to adverse biological effects such as altering the cellular redox status due to their pro-oxidative activity [1]. Reactive oxygen species are produced from several reactions within a cell and are closely regulated by a multiple biological network of protection [3] This network includes the antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), and endogenous antioxidants such as glutathione (GSH), vitamins E and C, and the β-nicotinamide adenine dinucleotide phosphate (NADPH) associated glutathione reductase (GR), as well as exogenous antioxidants including plant polyphenols [4]. Excessive exposure to polyphenols may overwhelm these antioxidant defense mechanisms in the cell, resulting in the over-production of reactive oxygen intermediates [2]. This contributes to cell injury and DNA damage, with the potential induction of irreversible pre-neoplastic lesions and carcinogenesis. Many uncertainties exist about the relative safe levels for such products

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