Dietary exposure to honeybush (Cyclopia) polyphenol-enriched extracts altered redox status and expression of oxidative stress and antioxidant defense-related genes in rat liver

Abstract

Interest in Cyclopia spp. (honeybush) as a source material for production of polyphenol-enriched extracts (PEEs) for the food ingredient and nutraceutical markets requires investigation of their safety. PEEs of Cyclopia subternata (PECsub) and Cyclopia genistoides (PECgen) were fed (2.5g/kg feed) to male Fischer rats for 28days, while PECsub, having the highest total polyphenol content and antioxidant activity, was also fed for 90days. Their dietary intake did not significantly (P≥0.05) affect body weight gain or relative liver and kidney weight. PECsub resulted in a significant (P<0.05) increase in the total serum bilirubin after 28days, while serum alkaline phosphatase levels were only significantly (P<0.05) increased after 90days, suggesting alterations in the biliary system. No effect on serum iron levels was noticed after 28days, but PECsub significantly (P<0.05) reduced serum iron after 90days. Both PECsub and PECgen increased glutathione reductase activity in the liver significantly (P<0.05) after 28days. Reduced glutathione (GSH) content was significantly (P<0.05) decreased after 90days by PECsub resulting in a marked, but not significant (P≥0.05) decrease in the GSH/GSSG ratio. Considering the expression of oxidative stress and antioxidant defense-related genes after 28days, the expression of eleven genes was altered by PECsub and PECgen. Seven genes, mutually affected by PECsub and PECgen, included (i) antioxidant-related genes, prostaglandin-endoperoxide synthase 1 (Ptgs1), kinesin family member 9 (Kif9) and serine (or cysteine) peptidase inhibitor clade B member 1b (Serpinb1b); (ii) genes involved in reactive oxygen species (ROS) metabolism, xeroderma pigmentosum complementation group A (Xpa) and thioredoxin interacting protein (Txnip) as well as (iii) oxygen transporter-related genes, Fanconi anemia complementation group C (Fancc) and vimentin (Vim). The expression of NADPH oxidase organiser 1 (Noxo1) increased 19.97-fold by PECsub and the thyroid peroxidase (Tpo) 372-fold by PECgen. Changes in the expression of the oxidative stress and antioxidant defense-related genes could be indicative of an underlying stress effected by the honeybush PEEs in the liver. Differential gene expression could likely be attributed to the differences in phenolic composition of the extracts. The daily dietary intake of total polyphenol and individual phenolic constituents, recalculated to a human equivalent dose, was much higher, especially for C. subternata, than normally consumed when habitually drinking “fermented” honeybush herbal tea. Subsequent studies verifying the protein-associated changes governing the oxidative status in the liver is required.