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Epidemiological studies have shown a consistent positive correlation between exposure to particulate matter (PM) and increased mortality largely due to increased rates of cardiovascular morbidity and mortality. Diesel exhaust particles (DEPs) are major constituents of atmospheric PM and have been shown to cause disruption of the endothelial cell monolayer integrity, thereby affecting organ functions. Endothelial cells are very active metabolic components of biological tissue that performs a number of important physiological functions. Therefore, anything that compromises the integrity and functions of the endothelium will lead to organ dysfunction and disease. This review focuses on scientific evidence that link DEP exposure to endothelial cell dysfunction in various pathophysiological conditions affecting the cardiovascular system. The various mechanisms involved in the DEP-induced endothelial cell dysfunction are also addressed together with the preventive and therapeutic approaches to overcoming these challenges.

Medicinal plants of the Plectranthus genus (Lamiaceae) are well known for their ethnomedicinal applications. Plectranthus madagascariensis, which is native to South Africa, is traditionally used in the treatment of respiratory conditions, scabies, and cutaneous wounds. The phytochemical studies of P. madagascariensis led to the isolation of five known royleanone abietanes, namely, 6&beta, 7&alpha, dihydroxyroyleanone (1), 7&alpha, acetoxy-6&beta, hydroxyroyleanone (2), horminone (3), coleon U quinone (4), and carnosolon (5). The relative configuration of compound 2 was established by X-ray analysis. Compounds 1&ndash, 4 showed antimycobacterial activity (Minimum inhibitory concentration for 90% inhibition, MIC90 = 5.61&ndash, 179.60 &mu, M) against Mycobacterium tuberculosis H37Rv. Compound 4 and 5 showed comparable toxicity (Concentration for 50% inhibition, IC50 98.49 &mu, M and 79.77 &mu, M) to tamoxifen (IC50 22.00 &mu, g/mL) against HaCaT cells. Compounds 1&ndash, 5 showed antioxidant activity through single-electron transfer (SET) and/or hydrogen-atom transfer (HAT) with compound 5 being the most active antioxidant agent. Compounds 3 and 5 were isolated for the first time from P. madagascariensis. The observed results suggest P. madagascariensis as an important ethnomedicinal plant and as a promising source of diterpenoids with potential use in the treatment of tuberculosis and psoriasis.

Rooibos (Aspalathus linearis), widely known as a herbal tea, is endemic to the Cape Floristic Region of South Africa (SA). It produces a wide range of phenolic compounds that have been associated with diverse health promoting properties of the plant. The species comprises several growth forms that differ in their morphology and biochemical composition, only one of which is cultivated and used commercially. Here, we established methodologies for non-invasive transcriptome research of wild-growing South African plant species, including (1) harvesting and transport of plant material suitable for RNA sequencing, (2) inexpensive, high-throughput biochemical sample screening, (3) extraction of high-quality RNA from recalcitrant, polysaccharide- and polyphenol rich plant material, and (4) biocomputational analysis of Illumina sequencing data, together with the evaluation of programs for transcriptome assembly (Trinity, IDBA-Trans, SOAPdenovo-Trans, CLC), protein prediction, as well as functional and taxonomic transcript annotation. In the process, we established a biochemically characterized sample pool from 44 distinct rooibos ecotypes (1&ndash, 5 harvests) and generated four in-depth annotated transcriptomes (each comprising on average &asymp, 86,000 transcripts) from rooibos plants that represent distinct growth forms and differ in their biochemical profiles. These resources will serve future rooibos research and plant breeding endeavours.

Aspalathin, the main polyphenol of rooibos (Aspalathus linearis), is associated with diverse health promoting properties of the tea. During fermentation, aspalathin is oxidized and concentrations are significantly reduced. Standardized methods for quality control of rooibos products do not investigate aspalathin, since current techniques of aspalathin detection require expensive equipment and expertise. Here, we describe a simple and fast thin-layer chromatography (TLC) method that can reproducibly visualize aspalathin in rooibos herbal tea and plant extracts at a limit of detection (LOD) equal to 178.7 ng and a limit of quantification (LOQ) equal to 541.6 ng. Aspalathin is a rare compound, so far only found in A. linearis and its (rare) sister species A. pendula. Therefore, aspalathin could serve as a marker compound for authentication and quality control of rooibos products, and the described TLC method represents a cost-effective approach for high-throughput screening of plant and herbal tea extracts.

Background: Rooibos types and forms and how prepared and flavoured influence the total polyphenol content and total antioxidant capacity (TAC). Aim: To denote an optimal rooibos cup as having the highest total polyphenol content and TAC, considering the different types, forms, preparation methods and flavourings and amounts (Phase 1), and determine the demographic, lifestyle and rooibos consumption characteristics of adult rooibos consumers, and the association of these characteristics with drinking the optimal cup (Phase 2). Setting: Assays: Oxidative Stress Research Centre, Cape Peninsula University of Technology; Consumer survey: George area, South Africa. Method: Phase 1 entailed determining the total polyphenol content (Folin–Ciocalteau method) and TAC (Trolox equivalent antioxidant capacity and ferric-reducing antioxidant power assay) of the prepared rooibos samples. For Phase 2, a developed, pilot tested questionnaire was used to profile adult rooibos consumers. Results: Phase 1: the following samples delivered higher total polyphenol content and TAC: green (type), green leaves and powdered extract (forms), and sample steeped for 10 min or longer (preparation method). The identified optimal cup was sample steeped for 10 min or longer. Phase 2: a total of 308 respondents completed the questionnaire. Few consumed more than one rooibos cup per day (25.3%; n = 78) and the optimal cup (15.9%; n = 49). These latter respondents comprised those who steeped rooibos in a teapot (not a cup or mug) ( p < 0.05). Conclusions: The optimal cup was identified as sample steeped for 10 min or longer. The rooibos consumers did not consume it sufficiently, nor steeped it long enough.

Aims Although there is evidence linking sugar-sweetened beverage (SSB) intake with the development of cardio-metabolic diseases, the underlying mechanisms remain unclear. The current study therefore evaluated the effects of SSB consumption by establishing a unique in-house in vivo experimental model. Main methods Male Wistar rats were divided into two groups: a) one consuming a popular local SSB (SSB- Jive), and b) a control group (Control-water) for a period of three and six months (n = 6 per group), respectively. Rats were gavaged on a daily basis with an experimental dosage amounting to half a glass per day (in human terms) (SSB vs. water). Cardiac function was assessed at baseline (echocardiography) and following ex vivo ischemia-reperfusion of the isolated perfused working rat heart. Oral glucose tolerance tests and mitochondrial respiratory analyses were also performed. In addition, the role of non-oxidative glucose pathways (NOGPs), i.e. the polyol pathway, hexosamine biosynthetic pathway (HBP) and PKC were assessed. Key findings These data show that SSB intake: a) resulted in increased weight gain, but did not elicit major effects in terms of insulin resistance and cardiac function after three and six months, respectively; b) triggered myocardial NOGP activation after three months with a reversion after six months; and c) resulted in some impairment in mitochondrial respiratory capacity in response to fatty acid substrate supply after six months. Significance SSB intake did not result in cardiac dysfunction or insulin resistance. However, early changes at the molecular level may increase risk in the longer term.

Antioxidant activities in Mytilus galloprovincialis were determined from samples collected at Scarborough, Hout Bay, Green Point, Milnerton and Bloubergstrand in Cape Town, South Africa. Antioxidant enzyme activity was determined by measuring CAT, SOD and GSH. The total antioxidant capacity was measured using FRAP and ORAC, while the content and lipid peroxidation marker levels of CDs and TBARS. Antioxidant activities and responses in mussels varied between sites with significant correlations for 85% and 71% of all antioxidant measurements made for Fe and Zn, respectively. The oxidative stress results reported here are novel for the region and indicated that mussels in Cape Town do not have (relatively) high levels of antioxidant activities as a result of exposure to metals. The research undertaken suggests that antioxidant responses was an appropriate biomarker of exposure to metals but more environmental parameters should be considered when interpreting antioxidant responses in the natural environment.

A 30-day exposure time experiment was designed to investigate whether the extent of physiological impacts of trihalomethane exposure on two Solanum lycopersicum cultivars correlated with either the number of bromine or chlorine atoms in the trihalomethane molecules, focusing on biomass gain, nutrient concentration, oxidative stress, fatty acids and α-tocopherol contents in membrane lipids. The gain of biomass in tomato seedlings decreased with an increase in the degree of bromination. Concentrations of essential nutrients required for plant growth such as nitrogen, phosphorus, potassium, sulphur and boron decreased in plant dry matter that correlated with the increasing number of chlorine atoms in the trihalomethane molecules. Trihalomethane exposure resulted in an increase in oxidative stress response in both tomato cultivars with parameters such as total phenolic content, ferric reducing antioxidant power, oxygen radical absorbance capacity and the activities of antioxidant peroxidase enzymes, all correlating with an increasing number of chlorine atoms in the trihalomethane molecule; hence, oxidative damage increased with a higher degree of chlorination. However, no such correlations were observed in superoxide dismutase activity, general lipid peroxidation, α-tocopherol content and total soluble proteins. In plant membrane lipids, an increase in the saturated fat hexadecanoic acid was observed in both tomato cultivars that correlated with the degree of chlorination in the trihalomethane molecule. The increase in α-linolenic acid stress signaling correlated with an increase in the degree of chlorination in only one tomato cultivar suggesting variable tolerance between cultivars to chemical action.

Ten flavonoid-related structures viz. heliteretifolin (1), isoxanthohumol (2), 2',4',6'-trihydroxy-3'-prenylchalcone (3), isoglabranin (4), glabranin (5), 7-methoxy-isoglabranin (6), quercetin (7), 4'-methoxyquercetin (8), 4'-methoxykaempferol (9) and mosloflavone (10) were isolated from a H. teretifolium methanolic extract and identified. One of them (compound 1) is reported for the first time from a natural source, while compounds 6, 8–10 were isolated for the first time from the genus Helichrysum. The total extract of H. teretifolium showed potent antioxidant activity. When tested for total antioxidant capacity compound 3 possesses moderate biological activity compared to 2, which displayed some of the highest TEAC values (4529.01 ± 2.44, 4170.66 ± 6.72) µM TE/g, respectively. Compounds 7 and 8 demonstrated the highest inhibitory activities on Fe2+-induced lipid peroxidation (IC50 = 2.931, 6.449 µg/mL), tyrosinase (8.092, 27.573) and elastase (43.342, 86.548). Additionally, the total antioxidant capacities measured as FRAP (4816.31 ± 7.42, 3584.17 ± 0.54) µM AAE/g, and ORAC for hydroxyl radical (7.265 ± 0.71, 6.779 ± 3.40) × 106 and peroxyl radical (17.836 ± 2.90, 12.545 ± 5.07) × 103 µM TE/g were also observed for compounds 7 and 8, respectively. In conclusion, H. teretifolium total extract represents a rich source of bioactive constituents with potent antioxidant and moderate anti-tyrosinase and anti-elastase activities that can help to avert accumulation of free radicals in the body, and could therefore be good candidates for the prevention and/or treatment of skin-related conditions, such as aging. This is the first scientific report on the chemical and biological profile of H. teretifolium.

Gethyllis multifolia is a South African bulbous geophyte with medicinal properties and on which very limited research has been conducted. This research investigated the effect of drought and shade, which are experienced in the natural habitat, on the antioxidant properties, as well as the isolation of natural compounds from certain plant parts. The total polyphenol, flavonol/flavone and flavanone contents, oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP) and radical cation scavenging ability (ABTS) were measured in the leaves, bulbs and roots (dry weight) of G. multifolia under photo- and drought stress. A significantly higher total polyphenol content was observed in the roots under the photo - and drought stresses when compared to the control. When all the plant parts were compared, the highest total polyphenol content was observed in the drought-stressed roots of G. multifolia . An increased antioxidant capacity was observed in the root system of G. multifolia where the FRAP, ORAC and ABTS were found to be significantly higher during drought stress when compared to the control. Phytochemical investigation of the leaves, bulbs and roots of G. multifolia revealed the presence of tannins, flavonoids, phenolics, saponins, glycosides (phenolic and terpenoid) as well as essential oils, while the test for alkaloids was negative. Further in -depth studies on the roots of G. multifolia led to the isolation of three known flavonoids, of which one was also isolated as its endogenously acetylated derivative. Their structures were elucidated by chemical and spectroscopic methods as 2,3-dihydro-7-hydroxy-2-phenyl-4 H -1-benzopyran-4-one ( 1 ), (1-[2.4-dihydroxyphenyl]-3-phenylpropan-1-one) ( 2 ), 2,3-dihydro-5,7-dihydroxy-2-phenyl-4 H -1-benzopyran-4-one or pinocembrin ( 3 ) and 5,7-diacetoxy-2,3-dihydro-2-phenyl-4 H -1-benzopyran-4-one ( 4 ). This investigation indicated how environmental conditions can be manipulated to enhance the antioxidant properties of certain plant parts for future cultivation of this species and the isolation of the four natural compounds elucidated its medicinal potential and created a platform for future in vivo research.

Previous evidence show foods and beverages rich in polyphenolic compounds to have favourable effects on the cardiovascular system.The current study assessed the modulation of oxidative stress and associated inflammation induced by diesel exhaust particles (DEP - SRM 2975) by pre-treatment of human umbilical vein endothelial cells (HUVECs) with aqueous extracts of rooibos [fermented (FR) as well as green form (GR)] and honeybush [fermented form (FH)].HUVEC are either exposed to DEP (10 µg/ml) for 4 h or pre-treated with 40 and 60 µg/ml of FR or GH or FR, or 50 µg/ml orientin (OR) for 6 h prior to DEP exposure.In vitro antioxidant capacity of the extracts was assessed and the polyphenol contents were also assessed by HPLC. ROS, cell viability, lactate dehydrogenase leakage, lipid peroxidation, GSH:GSSG ratios, conjugated diene and protein carbonyl levels were determined as indices of oxidative stress and cytotoxicity. RT-qPCR and western blot were used to assess inflammatory cytokines and antioxidant genes expression.DEP caused a dose and time-dependent increase in ROS production, significant (p 0.001) increase in protein carbonyl (PC) formation, thiobarbituric acid reactive substances and conjugated dienes levels (p 0.01) and a significant reduction in glutathione (GSH) redox status. Pre-incubation with either the herbal extracts or orientin attenuated these effects. The significant increase in IL-1α, IL-6, IL-8, VCAM-1 and ATF4 gene expression caused by DEP (10 µg/ml) were also attenuated by the presence of the FR, GR and FH extracts, and OR . Pre-treatment with the rooibos extracts or flavone orientin enhanced cell viability, reduced LDH leakage, enhanced mRNA expression of NQO1 and Nrf2, but repressed CYP1B1 mRNA induced by DEP. Western blot showed both the herbal tea extracts and orientin to enhance NQO1 and γGSC protein induction by DEP.Taken together, the herbal extracts offer protection against DEP-induced oxidative stress and inflammatory response.

Alcohol intake is associated with variation in many biochemical markers and metabolic processes implicated in car- diovascular disease (CVD) and other non-communicable diseases associated with advanced aging. Some changes are beneficial, while others may be harmful in relation to individual differences in genetic background. The objective of this study was to compare the effects of alternative moderate consumption of red wine and brandy on the lipid profile in the same experimental population of healthy adults and to identify genetic risk factors that may contribute to differences in response. An 8-week ran- domised crossover intervention study of red wine versus brandy consumption was performed in 37 healthy volunteers (19 males and 18 females) between the ages of 26 and 71 years. The assessments included anthropometric measurements, biochemical determinations and genetic analysis using a multi-gene CVD test. The level of total glutathione as an indicator of antioxidant capacity was significantly decreased only after the brandy intervention when compared to the baseline (p = 0.002). Both the brandy and wine intervention resulted in a significant increase in HDL-cholesterol (p < 0.001). Significant differential effects were shown in relation to genetic variation in the APOE (p = 0.027) and MTHFR (p = 0.048) genes, known to be associated with hyper-responsiveness to alcohol intake. Novel findings included a statistically significant increase of both total cholesterol (p = 0.016) and triglyceride (p = 0.022) levels with alcohol intake only in individuals who tested positive for the low-penetrance H63D and/or C282Y mutations in the HFE gene. This study confirmed the well-established protective effect of moderate alcohol consumption on the lipid profile, especially red wine. Since the genetic background influences the effect of alcohol on biochemical parameters of CVD risk, safe limits of wine and brandy consumption may in future be based partly on the genetic profile.

This study investigated the antioxidative effect of rooibos herbal tea and a rooibos-derived commercial supplement ontert-butyl hydroperoxide- (t-BHP-) induced oxidative stress in the liver. Forty male Wistar rats consumed fermented rooibos, unfermented rooibos, a rooibos-derived commercial supplement, or water for 10 weeks, while oxidative stress was induced during the last 2 weeks via intraperitoneal injection of 30 µmole oft-BHP per 100 g body weight. None of the beverages impaired the body weight gain of the respective animals. Rats consuming the rooibos-derived commercial supplement had the highest (P<0.05) daily total polyphenol intake (169 mg/day) followed by rats consuming the unfermented rooibos (93.4 mg/day) and fermented rooibos (73.1 mg/day). Intake of both the derived supplement and unfermented rooibos restored thet-BHP-induced reduction and increased (P<0.05) the antioxidant capacity status of the liver, while not impacting on lipid peroxidation. The rooibos herbal tea did not affect the hepatic antioxidant enzymes, except fermented rooibos that caused a decrease (P<0.05) in superoxide dismutase activity. This study confirms rooibos herbal tea as good dietary antioxidant sources and, in conjunction with its many other components, offers a significantly enhanced antioxidant status of the liver in an induced oxidative stress situation.

cope To determine the effect of Rooibos (Aspalathus linearis) on glucocorticoid biosynthesis and inactivation in vivo and in vitro. Methods and results Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analyses of in vivo studies showed that human Rooibos consumption increased cortisone plasma levels in males (p = 0.0465) and reduced cortisol:cortisone ratios in males and females (p = 0.0486) at risk for cardiovascular disease. In rats, corticosterone (CORT) (p = 0.0275) and deoxycorticosterone (p = 0.0298) levels as well as the CORT:testosterone ratio (p = 0.0009) decreased following Rooibos consumption. The inactivation of cortisol was investigated in vitro by expressing 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and type 2 (11βHSD2) in CHO-K1 cells. Rooibos inhibited 11βHSD1, which resulted in a significant reduction in the cortisol:cortisone ratio (p < 0.01). No significant effect was detected on 11βHSD2. In vitro studies in adrenal H295R cells showed that Rooibos and rutin, one of the more stable flavonoid compounds present in Rooibos, significantly reduced the levels of cortisol and CORT in cells stimulated with forskolin to mimic a stress response. Conclusion In vivo studies demonstrate that Rooibos significantly decreased glucocorticoid levels in rats and steroid metabolite ratios linked to metabolic disorders—cortisol:cortisone in humans and CORT:testosterone in rats. Results obtained at cellular level elucidate possible mechanisms by which these effects were achieved.

Gethyllis multifolia and Gethyllis villosa are winter-growing, summer-blooming, deciduous and bulbous geophytes that grow naturally in the semi-arid ‘Succulent Karoo Biome’ of South Africa. G. multifolia is threatened in its natural habitat and resides in the ‘Vulnerable’ category of the ‘Red Data List of Southern African Plants’. Previous investigations suggested that G. multifolia is more sensitive to drought stress than G. villosa and that both species adopted certain morphological changes in their leaves during shade stress. Current models indicate that this biome is being exposed to increasingly drier conditions and shading from encroaching indigenous plant species. In this study, the photosynthetic gas exchange responses of both species to drought and shade stresses were investigated and the ‘Vulnerable’ conservation status of G. multifolia. This investigation found that during drought stress G. villosa had a more enhanced photosynthetic performance than G. multifolia which appears not to be related to foliar adaptations such as specific leaf mass (SLM), but to the G. villosa's leaves maintaining their stomatal conductance (Gs), photosynthetic light compensation (LCP) and photon yields. Furthermore, during shade stress G. villosa also had an improved photosynthetic performance by not altering its photosynthetic LCP during reduced light conditions. It can be concluded that G. multifolia has a lower capacity than G. villosa to adapt its photosynthetic apparatus to changing environments such as increasing drought and shaded conditions. This may be a contributing factor to the threatened conservation status of G. multifolia.

Reactive oxygen species (ROS) are involved in many physiological functions of mammalian sperm. Numerous endogenous antioxidants belonging to both enzymatic and non-enzymatic groups can remove excess ROS and prevent oxidative stress (OS). This study compares the modulation of OS by rooibos, Chinese green tea and commercial rooibos and green tea supplements in rat sperm. Male Wistar rats (n = 60) were supplemented with fermented rooibos, ‘green’ rooibos, Chinese green tea, rooibos supplement, green tea supplement or water for 10 weeks while OS was induced during the last 2 weeks. Sperm count and motility were significantly higher for rats consuming fermented rooibos and ‘green’ rooibos when compared with the other groups. Catalase activity was significantly higher in the sperm of rats consuming fermented rooibos, ‘green’ rooibos and both the rooibos and green tea supplements. Superoxide dismutase concentration in the sperm of rats supplemented with fermented rooibos, ‘green’ rooibos and green tea was higher. Sperm glutathione levels of rats consuming the fermented and ‘green’ rooibos were also significantly higher. Rooibos fermented and ‘green’ rooibos showed a tendency to lower the levels of ROS and lipid peroxidation when compared with the control group. In conclusion, both rooibos extracts could offer a measure of protection against induced oxidative damage by increasing the antioxidant defence mechanisms and thereby improving the sperm quality and function. Copyright © 2012 John Wiley & Sons, Ltd.

A total of 43 individuals were included in a study of genetic and environmental factors associated with cardiovascular disease; seven subjects (16%) were diagnosed with the metabolic syndrome. A statistically significant association was observed between the E2 allele of the apolipoprotein E (Apo E) polymorphism and an increasing number of metabolic syndrome features (p = 0.03). Clinical and biochemical abnormalities identified could be ascribed to the combined effects of unfavorable genotypes and environmental factors known to interact with the Apo E gene. Excessive alcohol intake, high-calorie diets and smoking should be restricted in individuals with the Apo E2 and/or E4 alleles, which are associated with a significantly increased risk of cardiovascular disease.

This study investigated whether rooibos herbal tea Aspalathus linearis has an ergogenic effect during a fatiguing arm strength test to exhaustion. Thirty-two male participants were randomised in a single blinded, cross-over placebo controlled study in which they ingested standardised rooibos or placebo capsules for four weeks prior to a fatiguing elbow flexion/extension exercise test entailing five sets/bouts of 15 repetitions of maximum voluntary contractions separated by 10-second rest intervals on a Biodex System 3 at a speed of 60° per second. Peak torque flexion (Nm) was consistently higher in the rooibos experimental (Re) compared to the placebo control (Pc) across the five exercise bouts, and this performance trend during flexion was also seen in the total work (joules) completed, although not significant (P > 0.05). It appears that the antioxidant properties of rooibos, may have contributed to an improvement in physical performance during a maximal isokinetic arm exercise protocol to induce fatigue.

The chemoprotective properties of unfermented and fermented rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) herbal teas, and green and black teas (Camellia sinensis) were investigated against fumonisin B1 (FB1) promotion in rat liver utilizing diethylnitrosamine (DEN) as cancer initiator. The various teas differently affected the clinical chemical parameters associated with liver and kidney damage associated with FB1 suggesting specific FB1/iron/polyphenolic interactions. Green tea enhanced (P0.05) the FB1-induced reduction of the oxygen radical absorbance capacity, while fermented herbal teas and unfermented honeybush significantly (P0.05) decreased FB1-induced lipid peroxidation in the liver. The teas exhibited varying effects on FB1-induced changes in the activities of catalase, glutathione peroxidase (GPx) glutathione reductase (GR) as well as the glutathione (GSH) status. Unfermented rooibos and honeybush significantly (P0.05) to marginally (P0.1) reduced the total number of foci (10microm), respectively, while all the teas reduced the relative amount of the larger foci. Fermentation seems to reduce the protective effect of the herbal teas. Differences in the major polyphenolic components and certain FB1/polyphenolic/tissue interactions may explain the varying effects of the different teas on the oxidative parameters, hepatotoxic effects and cancer promotion in rat liver.

Reactive species are products of normal cellular metabolism and may be deleterious or beneficial. At low/moderate concentrations, reactive species are involved in physiological roles including cell signalling, defense against infectious agents and mitogenic responses. However, unbalanced defense mechanism of antioxidants, overproduction of reactive species or incorporation of free radicals into the living system from the environment may result in oxidative stress, a deleterious process that can lead to damage of important cell structures, including lipids and membranes, proteins and nucleic acids. The role of oxida‐ tive stress as a contributing factor in the pathophysiology of various diseases is increas‐ ingly being recognized, and augmenting the oxidative defense capacity of the cell through the intake of antioxidants as a way of preventing free radical-mediated cellular injuries is becoming a popular strategy. Much attention is being focused on the health beneficial role of phenolic phytochemicals derived from plants. They are considered to play an important role as physiologically functional foods and for the prevention of clini‐ cal conditions related to oxidative stress, even though their modes of action may still not be fully understood. Rooibos (Aspalathus linearis) is a popular South African tisane en‐ joyed for its taste and aroma. Rooibos has been made in the Cederberg mountain region of South Africa for generations and has been used medicinally for alleviation of allergies, asthma, infantile colic and skin problems. The potential antioxidative, immune-modulat‐ ing, chemopreventive and chemotherapeutic actions of rooibos have been reported in several studies. This review provides a comprehensive data on the current knowledge of the biological and chemotherapeutic activity of rooibos and its major flavonoids. Most re‐ cent in vitro and in vivo (animal and human) studies were conducted with special atten‐ tion paid to clinical conditions in which oxidative stress has been implicated. The conclusion described directions for future rooibos research to establish its activity and utility as a human chemopreventive and therapeutic agent.

Background: Cadmium (Cd) is a well known environmental and industrial toxicant causing damaging effects in numerous organs. In this study, we examined the role of heme oxygenase-1 (HO-1) in modulating the Cd-induced apoptosis in human hepatoma (HepG2) cells after 24 h exposure. Methods: HepG2 cells were exposed to 5 and 10 μM Cd as CdCl2 for 24 h while other sets of cells were pre-treated with either 10 μM Cobalt protoporphyrin (CoPPIX) or 10 μM Tin protoporphyrin (SnPPIX) for 24 h, or 50 μM Z-DEVD-FMK for 1 h before exposure to 5 and 10 μM CdCl2 for 24 h. Expressions of caspase 3, cytosolic cytochrome c, mitochondrial Bax and anti-apoptotic BCL-xl proteins were assessed by western blot. Intracellular reactive oxygen species (ROS) production was determined using the dihydrofluorescein diacetate (H2DFA) method. Cell viability was assessed by MTT assay, while a flow cytometry method was used to assess the level of apoptosis in the cell populations. Results: Our results show that there were a significant increase in the expression of cytosolic cytochrome c, mitochondrial Bax protein, and caspase 3 at 5 and 10 μM compared to the control, but these increases were attenuated by the presence of CoPPIX. The presence of SnPPIX significantly enhanced Cd-induced caspase 3 activities. CoPPIX significantly decreased the level of ROS production by 24.6 and 22.2 % in 5 and 10 μM CdCl2, respectively, but SnPPIX caused a significant increase in ROS production in the presence of CdCl2. HepG2 cell viability was also significantly impaired by 13.89 and 32.53 % in the presence of 5 and 10 μM CdCl2, respectively, but the presence of CoPPIX and Z-DEVD-FMK significantly enhanced cell survival, while SnPPIX enhanced Cd-impaired cell viability. The presence of CoPPIX and Z-DEVD-FMK also significantly decreased the population of apoptotic and necrotic cells compared with Cd. Conclusion: In summary, the present study showed that HO-1 attenuates the Cd-induced caspase 3 dependent pathway of apoptosis in HepG2 cells, probably by modulating Cd-induced oxidative stress.

Bioactive polyphenolics are ubiquitously present in plants and may play an important role in the prevention and management of certain human diseases. Three known flavonoids viz Kaemperol-3-O-rutinoside (1), quercetin-3-O-glucoside (2) and kaemperol-3-O-glucoside (3) and inseparable mixture (1:1) of quercetin-3-O-glucose/galactose (4) were isolated, and identified for the first time from Holarrhena floribunda. The antioxidant capacity using the ORAC, FRAP and TEAC assays and inhibition of lipid peroxidation were measured for isolated flavonoids. The result showed that compounds 2 and 4 showed significantly increased ORAC, TEAC, and FRAP activities with low pro-oxidant potential as well as improved lipid peroxidation inhibition levels when compared to compounds 1 and 3. The most active compounds were found to be flavonoids with a quercetin basic structure. These results imply that the isolated flavonoid glycosides are responsible for the antioxidant activity of the plant leaves and it forms the scientific basis for its traditional usage.

Antimutagenic activity of aqueous extracts of the South African herbal teas, Aspalathus linearis (rooibos) and Cyclopia spp. (honeybush) was compared with that of Camellia sinensis (black, oolong and green) teas in the Salmonella mutagenicity assay using aflatoxin B(1) (AFB(1)) and 2-acetylaminofluorene (2-AAF) as mutagens. The present study presents the first investigation on antimutagenic properties of C. subternata, C. genistoides and C. sessiliflora. The herbal teas demonstrated protection against both mutagens in the presence of metabolic activation, with the exception of "unfermented" (green/unoxidised) C. genistoides against 2-AAF, which either protected or enhanced mutagenesis depending on the concentration. Antimutagenic activity of "fermented" (oxidised) rooibos was significantly (P0.05) less than that of Camellia sinensis teas against AFB(1), while for 2-AAF it was less (P0.05) than that of black tea and similar (P0.05) to that of oolong and green teas. Antimutagenic activity of unfermented C. intermedia and C. subternata exhibited a similar protection as fermented rooibos against AFB(1). Against 2-AAF, fermented rooibos exhibited similar protective properties than unfermented C. intermedia and C. sessiliflora. Unfermented rooibos was less effective than the C. sinensis teas and fermented rooibos, but had similar (P0.05) antimutagenicity to that of fermented C. sessiliflora against AFB(1) and fermented C. subternata against 2-AAF. Fermented C. intermedia and C. genistoides exhibited the lowest protective effect against 2-AAF, while fermented C. intermedia exhibited the lowest protection when utilising AFB(1) as mutagen. Aspalathin and mangiferin, major polyphenols in rooibos and Cyclopia spp., respectively, exhibited weak to moderate protective effects when compared to the major green tea catechin, (-)epigallocatechin gallate (EGCG). Antimutagenic activity of selected herbal tea phenolic compounds indicated that they contribute towards (i) observed antimutagenic activity of the aqueous extracts against both mutagens and (ii) enhancement of the mutagenicity of 2-AAF by unfermented C. genistoides. Antimutagenic activity of the South African herbal teas was mutagen-specific, affected by fermentation and plant material, presumably due to changes and variation in phenolic composition.

In accordance with national and international regulatory standards, namely ISO/IEC 17025, the validation of chromatography methods is becoming necessary. This study provides an optimized and fully validated reversephase high performance liquid chromatography (RP-HPLC) assay with ultra-violet (UV) detection for the measurement of L-ascorbic acid (L-AA) in fruit, vegetable and food products. Several commercial fruit juices and teas, fresh fruit and vegetables and food extract products were analyzed using a high performance liquid chromatographic system with UV detection. Chromatographic separation of L-AA was achieved on a reverse phase C18 150 mm×4.6 mm, 0.5 μm column with UV detection of 245 nm at room temperature. Distilled water/acetonitrile/formic acid (99: 0.9: 0.1, v/v/v) at a flow rate of 1 mLmin-1 was used as the mobile phase, in isocratic mode. Samples were extracted in 4.5% metaphosphoric acid solution and filtered through a 0.45 μm membrane. The method was validated for accuracy, precision, linearity, range, limit of detection, limit of quantification, specificity, stability, robustness and system suitability in accordance with ISO 17025 validation requirements. Validation results demonstrated a linear response within a range of 5 to 125 μg/mL with a correlation coefficient of 0.999 was obtained. Mean recoveries ranged from 99 to 103% and 92 to 96% for L-AA standards and samples, respectively. The method was found to be precise (COV’s

The South African fynbos plant, Aspalathus linearis (Brum.f) Dahlg. (Fabaceae, Tribe Crotalarieae), is traditionally used as a herbal tisane referred to as rooibos or redbush. This plant has claimed medicinal properties based mostly on anecdotal evidence. Rooibos is naturally caffeine free and contains a unique blend of polyphenolic compounds. Based on its in vitro antioxidant potential, a few studies also suggest modulation of oxidative stress/damage by rooibos extracts in experimental animals. More recent studies have examined the bioactivity of rooibos in humans. Together, these factors have contributed to the popularity of

This study compares the modulation of oxidative stress by an indigenous herbal tea, rooibos, Chinese green tea and commercial rooibos and green tea supplements in rat testicular tissue. Male Wistar rats (n = 60) were fed with either fermented rooibos, “green” rooibos, Chinese green tea, commercial rooibos or green tea supplements for ten weeks. Oxidative stress (OS) was induced in all animals by an intraperitoneal t-butyl hydroperoxide injection in the last two weeks of the study. The superoxide dismutase (SOD) activity increased significantly (P < 0.05) in the testicular tissue of rats that consumed fermented rooibos, green tea and rooibos supplement as compared to the control. The glutathione levels of rats that consumed the green tea supplement was also significantly (P < 0.05) increased when compared with the control. Reactive oxygen species (ROS) levels were significantly (P < 0.05) decreased in rats that consumed the rooibos supplement, while lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) was significantly (P < 0.05) decreased in rats that consumed fermented rooibos and green tea. In conclusion, both extracts of fermented rooibos and green tea could be effective in the protection of testicular tissue against oxidative damage by possibly increasing the antioxidant defense mechanisms in rats, while reducing lipid peroxidation.Key words: Antioxidants, epididymal sperm, catalase, glutathione, green tea (Camellia sinensis), lipid peroxidation, oxidative stress, reactive oxygen species, rooibos (Aspalathus linearis), superoxide dismutase.

Aim & background Phlorotannins are a family of polyphloroglucinols with numerous biological activities including anticancer, antimalarial and antioxidant. They are highly sought for utilization in food ingredients, animal feeds, fertilizers and medicines. This work reports the isolation, from brown algae, of four phlorotannin derivatives namely phloroglucinol (1), eckol (2), 7-phloroeckol (3) and 2-phloroeckol (4). Their radical scavenging activity was assayed to elucidate their capacity to scavenge free radical species. Their structural and electronic features were then compared across structures to provide an explanation for the differences in their radical scavenging properties. Moreover, the two main radical scavenging mechanisms, namely hydrogen atom transfer (HAT) and electron transfer (ET), were checked to determine the preferred mode of radical scavenging. Methods Polyphenols were determined spectrophotometrically according to the Folin–Ciocalteu colorimetric methods and the antioxidant assays were determined by means of ORAC assay and the Trolox equivalent antioxidant capacity (TEAC) assay. Theoretical studies were performed by means of the Density Functional Theory (DFT) method. Results Theoretical predictions indicate that the radical scavenging activities follow the order 1 Conclusion Overall, the results suggest that the position of substitution of phloroglucinol unit on eckol (2) plays a significant role in determining the radical scavenging ability of the resulting eckol derivatives.

Persistent immune activation characterises HIV infection and is associated with depletion of CD4+ T-cells and increased risk of disease progression. Early loss of gut mucosal integrity results in the translocation of microbial products such as lipopolysaccharide (LPS) into the systemic circulation. This is an important source of on-going immune stimulation. The purpose of this study was to determine levels of CD4+ T-cell activation (%CD25 expression) and apoptosis (% annexin V/7-AAD) in asymptomatic, untreated HIV infection at baseline and after stimulation with LPS and incubation with or without vitamin C and N-acetylcysteine. LPS induced a significant (P<0.03) increase in %CD25 expression, annexin V, and 7-AAD in HIV positive individuals. NAC in combination with vitamin C, significantly (P=0.0018) reduced activation and early apoptosis of CD4+ T-cells to a greater degree than with either antioxidant alone. Certain combinations of antioxidants could be important in reducing the harmful effects of chronic immune activation and thereby limit CD4+ T-cell depletion. Importantly, we showed that CD4+ T-cells of the HIV positive group responded better to a combination of the antioxidants at this stage than those of the controls. Therefore, appropriate intervention at this asymptomatic stage could rescue the cells before repetitive activation results in the death of CD4+ T-cells.

Widespread consumption of herbal teas has stimulated interest in their role as cancer preventive agents. The present investigation monitored the modulation of methylbenzylnitrosamine (MBN)-induced esophageal squamous cell carcinogenesis by rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) herbal and Camellia sinensis teas in male F344 rats. The tumor multiplicity was significantly (P0.05) inhibited by unfermented honeybush (45.5%), green (50%), and black (36%) teas, while the other teas exhibited weaker effects (30% inhibition). The mean total papilloma size was reduced by unfermented rooibos (87%), unfermented honeybush (94%), and fermented honeybush (74%) due to the absence of large papillomas (10 mm(3)). Reduction of the mean total papilloma number correlated with the total polyphenol (TPP) (r = 0.79; P0.02) and flavanol/proanthocyanidin (FLAVA) (r = 0.89; P0.008) intake (mg/100 g body weight) of the teas and the FLAVA (r = 0.89; P0.04) and flavonol/flavones/xanthones (r = 0.99; P0.002) intake when considering only the herbal teas. A daily TPP intake threshold of 7 mg/100 g body weight existed below where no inhibition of papilloma development was observed. Fermentation of herbal teas reduced the inhibitory effects on papilloma development associated with a reduction in the polyphenolic constituents. The inhibitory effect of herbal teas on papilloma development is associated with different flavonoid subgroups and/or combination thereof.

Rooibos, a unique South African herbal tea, is known to be an important source of unique polyphenolic compounds. In the present study we have quantified the main polyphenolic compounds in both fermented/traditional and unfermented/"green" rooibos (Aspalathus linearis) and evaluated its cardioprotective effects against ischaemia/reperfusion injury. Male Wistar rats consumed aqueous rooibos and green tea (Camellia sinensis) extracts (2%, w/v) for 7 weeks before their hearts were rapidly excised and perfused in a working heart perfusion apparatus. The results showed that the rooibos supplemented hearts significantly improved aortic output recovery after reperfusion when compared to the green tea supplemented hearts. Additionally, we showed that the rooibos extracts, containing the highest amount of flavonols, significantly decreased the level of cleaved caspase-3 and PARP, both pro-apoptotic proteins, during reperfusion when compared to green tea. Green tea supplementation increased phosphorylation of total PKB/Akt, Akt (threonine 308) and Akt (serine 473). The rooibos extracts did not cause significant change in the levels of the pro-survival PKB/Akt (threonine 308 and serinet 473). The GSH/GSSG ratio in the hearts of the green tea supplemented group was significantly (p

The possible mechanism of photoprotection by polyphenolic extracts of honeybush and the two most abundant polyphenols found in honeybush, hesperidin and mangiferin were determined using a mouse model. Ethanol: acetone soluble extracts and pure honeybush compounds were applied topically to the skin of SKH-1 mice before daily exposures to ultraviolet B (UVB) (180 mJ/cm²) for 10 days. The honeybush extracts reduced signs of sunburn, such as erythema, peeling and hardening of the skin and also significantly (P < 0.05) reduced edema, epidermal hyperplasia and the induction of cyclooxygenase-2 (COX-2), ornithine decarboxylase (ODC), GADD45 and OGG1/2 expression. The fermented honeybush extract significantly (P < 0.05) reduced lipid peroxidation and depletion of the antioxidant enzymes catalase and superoxide dismutase. Hesperidin and mangiferin were less effective. These results show that extracts of honeybush and to some extent, hesperidin and mangiferin, renders protection against UVB-induced skin damage. The mechanisms investigated suggest that honeybush extracts protected the skin via modulation of induced-oxidative damage, inflammation and cell proliferation. Other specific biological properties such as modulation of signaling pathways could also be involved.

In South Africa, the plant Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is traditionally used as a "tea" referred to as rooibos or redbush. This plant has been listed as a medicinal plant based mostly on anecdotal evidence.Despite a long history of traditional use in South Africa, very little scientific data are available from controlled clinical trials confirming its popular use. The aim of the present study was to investigate the effect of rooibos on biochemical and oxidative stress parameters in adults at risk for cardiovascular disease.After a washout period of 2 weeks, 40 volunteers consumed six cups of fermented/traditional rooibos daily for 6 weeks, followed by a control period. Blood biochemical parameters indicative of antioxidant activity and content (total polyphenols), lipid peroxidation (conjugated dienes - CDs, thiobarbituric acid reactive substances - TBARS), redox status (total glutathione - tGSH, ratio of reduced to oxidized glutathione - GSH:GSSG), lipid profile (total cholesterol, low density lipoprotein - LDL and high density lipoprotein - HDL cholesterol and triacylglycerol levels) and liver and kidney function were measured at the end of each study period.Plasma antioxidant capacity was not altered, but plasma total polyphenol levels increased significantly after rooibos consumption compared with the control levels (from 79.8±16.9 mg/L to 89.8±14.1 mg/L). Significant decreases in plasma markers of lipid peroxidation were found after rooibos consumption, as reported by levels of CDs (167.3±29.5 nmol/mL vs. 108.8±20.1 nmol/mL) and TBARS (1.9±0.6 μmol/L vs. 0.9±0.3 μmol/L). Reduced glutathione (797±238 μmol/L vs. 1082±140 μmol/L) and the GSH:GSSG ratio (41±14 vs. 76±17) were both significantly increased after consumption of rooibos. The lipid profiles showed that rooibos consumption, compared with the control values, significantly decreased serum LDL-cholesterol (4.6±1.3 mmol/L vs. 3.9±0.7 mmol/L) and triacylglycerols (1.7±0.8 mmol/L vs. 1.2±0.7 mmol/L), while HDL-cholesterol (0.9±0.1 mmol/L vs. 1.2±0.2 mmol/L) was significantly increased.Confirming its popular use, consumption of fermented, traditional rooibos significantly improved the lipid profile as well as redox status, both relevant to heart disease, in adults at risk for developing cardiovascular disease.

Rooibos (Aspalathus linearis (Brum.f.) Dahlg.) and honeybush (Cyclopia Vent. species) have a long history of traditional uses in South Africa as indigenous herbal health beverages or tisanes. These herbal teas are rich in several unique polyphenolic compounds that not only differ from that of Camellia sinensis teas, but also from one another. The bioactivity of both includes in vitro and in vivo antimutagenic, antioxidant, cancer modulating, cardiovascular and other activities. The first clinical controlled study which showed that rooibos decreased oxidative lipid damage and increased the redox status in plasma is discussed while human studies on honeybush have not yet been studied to date.

The antioxidant properties of the fruit of the Rosa roxburghii (RR) plant have been associated with several putative health promoting effects. The possible cytotoxic, mutagenic/antimutagenic and genotoxic effects of RR fruit extract were investigated. The effect on antioxidant status and protection against induced oxidative stress were also investigated using primary rat hepatocytes. A RR fruit extract containing 45 g/L total ascorbic acid and 65 g/L total polyphenols was used in this study. Dilutions up to 0.08% (v/v) increased significantly the antioxidant status in primary rat hepatocytes. The glutathione redox state was decreased with RR treatment but was increased in Chang liver cells and MT-2 lymphoblast. No cyto- or genotoxicity were observed at levels of up to 5% (v/v) of the fruit extract. In addition, a significant protection against t-BHP induced oxidative stress was observed in primary rat hepatocytes. The Ames test revealed no mutagenic activity using the Salmonella typhimurium strains TA98, TA100 and TA102. A significant antimutagenic effect of the extract was observed against the metabolic activated mutagens 2-acetylaminofluorene and aflatoxin B1 and to a lesser extent against methyl methanesulfonate. It is concluded that these results support the associated health promoting potential of Rosa Roxburghii fruit and in particular against oxidative stress. Copyright © 2007 John Wiley & Sons, Ltd.

Background: This study investigated the hepatic, renal and endogenous antioxidant status modulatory effects of chronic cosupplementation of rooibos and red palm oil (RPO) in male Wistar rats. Materials and Methods: Rats were randomized into four groups (n=10/group) and fed daily either standard rat chow (SRC) and water ( Group I ), SRC and the aqueous rooibos extract (2% w/v; ( Group II ), SRC and RPO (200 μL/day) with water ( Group III ), or SRC and RPO (200 μL/day) with rooibos (2% w/v; Group IV ) for 22 weeks. Results: Chronic feeding of rooibos, RPO or their combination did not induce any adverse hepatic or renal effects, as shown by serum levels of alkaline phosphatase, alanine- and aspartate aminotransferase, lactate dehydrogenase, albumin, creatinine, blood urea nitrogen and uric acid. Histopathology analyses showed that liver from the three supplementation groups displayed normal hepatic histoarchitecture. Chronic feeding of RPO did not influence the redox status in the blood and liver significantly. Supplementation of rooibos alone for 22 weeks significantly (P

The modulating effect of ethanol/acetone (E/A) soluble fractions, prepared from methanolic extracts of processed and unprocessed rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) as well as green (Camellia sinensis) teas was established in a two-stage mouse skin carcinogenesis assay. Topical application of the tea fractions prior to the tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), on ICR mouse skin initiated with 7,12-dimethylbenz[a]anthracene (DMBA) suppressed skin tumorigenesis significantly (P

Rooibos and honeybush teas significantly (P < 0.05) enhanced the activity of cytosolic glutathione S-transferase alpha. A significant (P < 0.05) to marginal (P < 0.1) increase in the activity of the microsomal UDP-glucuronosyl transferase was obtained with unprocessed rooibos and honeybush teas, respectively. Oxidized glutathione (GSSG) levels were significantly (P < 0.05) reduced in the liver of all tea treated rats while reduced glutathione (GSH) was markedly increased in the liver of the herbal tea treated rats. These changes resulted in a significant (P < 0.05) increase in the GSH/ GSSG ratio by the unprocessed, processed rooibos and unprocessed honeybush teas. Green and black teas markedly to significantly decreased the oxygen radical absorbance capacity in liver homogenates, respectively. Modulation of phase II drug metabolizing enzymes and oxidative status in the liver may be important events in the protection against adverse effects related to mutagenesis and oxidative damage.

The antimutagenic properties of South African herbal teas were investigated using the Salmonella typhimurium mutagenicity assay. Aqueous extracts of fermented and unfermented rooibos tea (Aspalathus linearis) and honeybush tea (Cyclopia intermedia) both possess antimutagenic activity against 2-acetylaminofluorene (2-AAF) and aflatoxin B1 (AFB1)-induced mutagenesis using tester strains TA98 and TA100 in the presence of metabolic activation. A far less inhibitory effect was noticed against the direct acting mutagens, methyl methanesulfonate (MMS), cumolhydroperoxide (CHP), and hydrogen peroxide (H2O2) using TA102, a strain designed to detect oxidative mutagens and carcinogens. Depending on the mutagen used, the unfermented tea exhibited the highest protective effect. A similar response regarding the protection against mutagenesis was obtained when utilising different variations of the double layer Salmonella assay. The double layer technique proved to be more effective to detect the protective effect of the different tea preparations against the direct acting mutagens. With respect to indirect mutagens, the highest protection was noticed when the carcinogen was metabolically activated in the presence of the tea extract as compared with when the tea extract was incubated in a separate layer with the bacteria. The current data suggest that two mechanisms seem to be involved in the antimutagenicity of the tea extracts towards carcinogens that require metabolic activation: (i) the tea components may interfere with cytochrome P450-mediated metabolism of these mutagens and (ii) the direct interaction between the tea constituents, presumably the polyphenolic compounds, with the promutagens and/or the active mutagenic metabolites. However, the mild and/or lack of protection and in some cases even enhancement of mutagenesis induced by direct acting or oxidative mutagens, provide new perspectives regarding the role of the polyphenolic compounds known to exhibit antioxidant properties, in the protection against mutagenesis in the Salmonella assay. The present study provides the first evidence on the antimutagenic activity of honeybush tea and further evidence on the antimutagenicity of rooibos tea.

Background Acute liver injury occur after intraperitoneal administration of lipopolysaccharide (LPS). Oxidative stress and release of pro-inflammatory cytokines are both implicated in the pathogenesis of LPS-induced acute liver injury. This study investigated the ameliorative effect of fermented rooibos (Aspalathus linearis) extract on LPS-induced acute liver injury. Method Major phenolic compounds in the fermented rooibos extract by HPLC-DAD, as well as the in vitro antioxidant capacity were quantified before the start of the experiment. Male Wistar rats were randomized into 4 groups (n = 10 per group) and given either water or fermented rooibos extract for 4 weeks before LPS injection. Hepatic function markers, including aminotransferases and lactate dehydrogenase, lipid peroxidation markers, antioxidant enzymes, glutathione redox status, as well as cytokine levels were monitored in the rats. Results Injection of LPS significantly increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Oxidative stress, evidenced by increased thiobarbituric acid reactive substances (TBARS) measured as malondialdehyde (MDA) in plasma and liver, and decreased glutathione redox status (GSH: GSSG ratio) in whole blood and liver was induced in LPS-challenged rats. Furthermore, hepatic levels of pro-inflammatory response markers TNF-α, IL-1β and IL-6 were increased significantly. Pre-feeding the fermented rooibos extract for 4 weeks decreased LPS-induced elevated levels of serum AST and LDH (significantly, p

We review the hepatocarcinogenic effects of fungal cultures of Fusarium verticillioides(= Fusarium moniliforme) strain MRC 826 in male BD IX rats. Subsequent chemical analyses of the fumonisin B (FB) mycotoxin content in the culture material used and long-term carcinogenesis studies with purified FB1 provide information about dose-response effects, relevance of hepatotoxicity during FB1-induced carcinogenesis, and the existence of a no-effect threshold. Fumonisin intake levels of between 0.08 and 0.16 mg FB/100 g body weight (bw)/day over approximately 2 years produce liver cancer in male BD IX rats. Exposure levels < 0.08 mg FB/100 g bw/day fail to induce cancer, although mild toxic and preneoplastic lesions are induced. The nutritional status of the diets used in the long-term experiments was marginally deficient in lipotropes and vitamins and could have played an important modulating role in fumonisin-induced hepatocarcinogenesis. Short-term studies in a cancer initiation/promotion model in rat liver provided important information about the possible mechanisms involved during the initial stages of cancer development by this apparently nongenotoxic mycotoxin. These studies supported the findings of long-term investigations indicating that a cytotoxic/proliferative response is required for cancer induction and that a no-effect threshold exists for cancer induction. The mechanisms proposed for cancer induction are highlighted and include the possible role of oxidative damage during initiation and the disruption of lipid metabolism, integrity of cellular membranes, and altered growth-regulatory responses as important events during promotion.

Background Red palm oil (RPO) and rooibos have been shown to exhibit cardioprotective properties. RPO is rich in essential fatty acids and fat soluble antioxidants while rooibos contains polyphenolic compounds with a unique composition of flavonoids. They exert their biological effects in different cellular compartments. Therefore the combination of these two natural food compounds has the potential to enhance the spectrum of available dietary antioxidants in different cellular compartments, which could result in an enhanced protection against certain pathological conditions such as inflammation. Methods Male Wistar rats weighing 150-200 g were supplemented with RPO, rooibos or their combination for 28 days. The Langendorff system and the lipoposaccharide (LPS)-induced inflammatory model were used to establish if RPO and rooibos, when supplemented alone or in combination, will reverse the negative effects of LPS on cardiac function at baseline. The effect of dietary intervention was also investigated on modulation of pro-inflammatory and anti-inflammatory cytokines in plasma and myocardial tissue. Results and discussion The LPS resulted in induction of systemic inflammation as evidenced by increased levels of IL-1β in plasma of LPS-treated rats compared to their non-treated control counterparts. Dietary supplementation and LPS treatment did not have an effect on baseline cardiac functional parameters. However, the elevation of IL-1β levels in plasma of LPS-induced rats consuming either RPO or rooibos alone were paralleled with increased levels of the anti-inflammatory cytokine, IL-10. The combination of rooibos and RPO was associated with enhanced endogenous production of myocardial IL-10 in LPS-induced rats. Conclusion The results of this study indicate that RPO and rooibos when supplemented individually showed anti-inflammatory effect at systemic level while their combination exhibited an enhanced anti-inflammatory effect in the myocardial tissue. Therefore, the findings in the current study argue that the combination of these two natural food substances could be beneficial in clinically relevant conditions where inflammation plays a role.