Cancer modulating properties of unique South African herbal teas (rooibos and honeybush) in short term in vitro and in vivo carcinogenesis assays

[摘要] ENGLISH ABSTRACT: This thesis provides the first scientific evidence on the cancer modulating properties oftwo unique South African herbal teas, rooibos (Aspalathus Iinearis) and honeybush(Cyclopia intermedia) utilizing in vitro as well as in vivo carcinogenesis assays by:• Demonstrating the in vitro antimutagenic activity of aqueous extracts of theherbal teas against the metabolic activated mutagens, 2-acetylaminofluorene (2-AAF) and the mycotoxin, aflatoxin B1 (AFB,) as well as, to a certain extent,against the direct acting mutagen, hydrogen peroxide, utilizing the Salmonellatyphimurium mutagenicity assay.• Increasing the activity of hepatic drug metabolizing enzymes, glutathione Stransferasealpha and UPD-glucuronosyl transferase, and reduced the oxidativestress by stabilizing the level of reduced glutathione (GSH) resulting in anincreased hepatic reduced to oxidized glutathione ratio (GSG:GSSG). No toxiceffects were noticed in rats consuming the herbal teas for 10 weeks as their solesource of drinking fluid.• Demonstrating the ex vivo modulation of 2-AAF- and AFB1-induced mutagenesisby sub- cellular hepatic fractions of rats consuming the herbal teas in theSalmonella mutagenicity assay. Hepatic cytosolic fractions protected againstmutagenesis of both mutagens, while the microsomal fractions exhibited areduced capacity to metabolize AFB1 to its active mutagenic metabolite.• Providing evidence for the in vivo modulation of tumour promotion using the liveras well as the two-stage skin carcinogenesis animal models. The unprocessedherbal teas arrested proliferation of the placental form of glutathione-Stransferase(GSTP+) altered cells as well as reduced the total number of enzymealtered foci in the liver of rats. Topical application of polyphenolic fractions of thevarious herbal teas prior to 12-0-tetra-decanoylphorbol-13-acetate (TPA) tumourpromotion, reduced tumour formation in mouse skin initiated with 7,12-dimethylbenz[ajanthracene (DMBA). The protective effect was illustrated by a decreasedtumour incidence, a reduction in tumour volume as well as a delayed onset of tumour development. The f1avanol/proanthocyanidin content of the fractionscould playa major role in the protection against skin tumour promotion.• Proposing possible mechanisms whereby rooibos and honeybush herbal teascould exert their cancer modulating properties with respect to in vitro and ex vivoantimutagenicity, in vivo oxidative status and reduced tumour promotion.• Providing evidence that the herbal teas mimic the cancer modulating propertiesof green and black teas although differences exist, presumably due to differencesin the polyphenolic constituents.• Suggesting that rooibos and honeybush herbal teas may play an important roleas chemopreventive agents in the modulation of cancer.

[发布机构] Stellenbosch University