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• RB stunted the adverse effects of isoproterenol. • RB reduced cell size, improved antioxidant enzyme activity, and improved mitochondrial function. • RB increased the expression of total Akt and reduced NFAT expression. • The protective effects of RB are ascribed to its potent antioxidant action and rescuing effect on mitochondrial dysfunction. Cardiovascular disease (CVD) is a global health threat associated with several risk factors, including systemic hypertension. Persistent elevation in blood pressure exerts significant stress on the left ventricle, which can lead to left ventricular hypertrophy and over time, progress to left ventricular failure. Most pharmacological treatments have long-term side effects and are costly, especially for patients who reside in low-resource settings. Therefore, there is a quest to identify adjuvant therapies that are more natural and affordable, to assist in managing CVD. This study aimed to evaluate the protective effects of Aspalathus linearis (Rooibos, RB) against isoproterenol-induced hypertrophy in H9c2 cardiomyoblasts. Cardiomyoblasts were exposed to either isoproterenol (50 μM, 24 h), RB (100 μg/mL, 24 h), co-treatment with isoproterenol (50 μM, 24 h) and control (2 % FBS media, 24 h). We conducted the following experiments: cell viability assay (MTT), cell size (light microscopy), antioxidant assays (SOD and CAT), lipid peroxidation assay (TBARS), Western blots, high-resolution respirometry and an ATP assay. Isoproterenol increased cell size, reduced cell viability, reduced the activities of SOD and CAT, increased oxidative stress via an increase in lipid peroxidation, reduced mitochondrial routine respiration, complex-I linked OXPHOS and the contribution of complex-II to the ETS via the S-pathway, and elevated complex-IV activity without negatively impacting ATP levels. Co-treatment with RB and isoproterenol reduced cell size, improved antioxidant enzyme activity, increased routine respiration, increased complex-I linked OXPHOS, and reduced the cytochrome-c response, while increasing the expression of total Akt and reducing total NFAT expression. Our data suggests that RB may be a potential adjuvant therapy in treating left ventricular hypertrophy. The protective effect of RB in this context is ascribed to its potent antioxidant action and rescuing effect on mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

High dose of fluoride intake is associated with toxic effects on kidney and cardiac tissues. This study evaluated the potential protective effect of fermented rooibos tea (RTE) on sodium fluoride (NaF)-induced cardiorenal toxicity in rats. Male Wistar rats (n = 56) were randomly allocated into one of seven equal groups: control, NaF (100 mg/kg orally), NaF + RTE (2%, w/v), NaF + RTE (4%, w/v), NaF + lisinopril (10 mg/kg orally), 2% RTE, and 4% RTE. The experiment lasted for 14 days and RTE was administered to the rats as their sole source of drinking fluid. NaF induced cardiorenal toxicity indicated by elevated level of urea, creatinine, LDH, creatinine kinase-MB, and cardiac troponin I in the serum, accompanied by altered histopathology of the kidney and heart. Furthermore, levels of H2O2, malondialdehyde, and NO were elevated, while GSH level was depleted in the kidney and heart due to NaF intoxication. Protein levels of c-reactive protein, TNFα, IL-1B, and NF-κB were increased by NaF in the serum, kidney, and heart. RTE at 2% and 4% (w/v) reversed cardiorenal toxicity, resolved histopathological impairment, attenuated oxidative stress and inhibited formation of pro-inflammatory markers. RTE at both concentrations down-regulates the mRNA expression of NF-κB, and upregulates the mRNA expression of both IκB and IκKB, thus blocking the activation of NF-κB signaling pathway. Taken together, these results clearly suggest that the protective potential of rooibos tea against NaF-induced cardiorenal toxicity, oxidative stress, and inflammation may be associated with the modulation of the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Leydig cells are essential for steroidogenesis and spermatogenesis. An imbalance in the production of reactive oxygen species (ROS) and the cellular antioxidant level brings about oxidative stress. Oxidative stress (OS) results in the dysfunction of Leydig cells, thereby impairing steroidogenesis, spermatogenesis, and ultimately, male infertility. To prevent Leydig cells from oxidative insults, there needs to be a balance between the ROS production and the cellular protective capacity of antioxidants. Evidence indicates that medicinal plants could improve Leydig cell function at specific concentrations under basal or OS conditions. The increased usage of medicinal plants has been considered a possible alternative treatment for male infertility. This review aims to provide an overview of the impact of oxidative stress on Leydig cells as well as the effects of various medicinal plant extracts on TM3 Leydig cells. The medicinal plants of interest include Aspalathus linearis, Camellia sinensis, Moringa oleifera, Morinda officinale, Taraxacum officinale, Trichilia emetica, Terminalia sambesiaca, Peltophorum africanum, Ximenia caffra, Serenoa repens, Zingiber officinale, Eugenia jambolana, and a combination of dandelion and fermented rooibos (CRS-10). According to the findings obtained from studies conducted on the evaluated medicinal plants, it can, therefore, be concluded that the medicinal plants maintain the antioxidant profile of Leydig cells under basal conditions and have protective or restorative effects following exposure to oxidative stress. The available data suggest that the protective role exhibited by the evaluated plants may be attributed to their antioxidant content. Additionally, the use of the optimal dosage or concentration of the extracts in the management of oxidative stress is of the utmost importance, and the measurement of their oxidation reduction potential is recommended. [ABSTRACT FROM AUTHOR]

Oxidative stress due to obesity plays a detrimental role in the testicular microenvironment and sperm parameters. We explored the impact of a hypercaloric diet in male BALB/c mice as a condition to trigger damage to the spermatogenic process and the antioxidant effect of Aspalathus linearis as well. We used a hypercaloric diet in animals divided into 3 groups: Control, Hypercaloric diet control (HC) and Hypercaloric diet and Rooibos infusion (HCR). Morphometric parameters, enzyme dosages, cell viability, and tubular histopathology were evaluated. Body weight increased in HCR animals at weeks 3, 4, and 8. We found a reduction in seminiferous epithelium height, with an increase in the tubular diameter of the HCR group. Catalase levels were lower in HC and HCR, while carbonyl protein was decreased in HC. We estimate that it induces oxidative stress (OS) capable of affecting the seminiferous epithelium and that the infusion of A. linearis does not demonstrate a potential benefit in cell preservation. [ABSTRACT FROM AUTHOR]

• Oxidative stress biomarkers are attenuated by REE in a glucotoxic HepG2 cell model. • REE enhances antioxidant enzyme profiles of HepG2 cells exposed to high glucose. • REE activates NRF2 antioxidant pathway in HepG2 cells exposed to high glucose. The exposure of hepatocytes to high concentrations of glucose results in a glucotoxic environment and ensuing hepatocellular injury, often due to oxidative stress. The popularly consumed herbal tea, Rooibos (Aspalathus linearis), demonstrates pleiotropic pharmacological and antioxidant activities. Our study investigated the molecular events regulating the antioxidant effects of a Rooibos ethanolic extract (REE) in a glucotoxic HepG2 liver cell model. It is hypothesized that REE enhances antioxidant enzyme profiles of HepG2 cells exposed to high glucose to attenuate glucotoxic damage. Glucotoxicity was induced by treating the cells with 25 mM glucose. For this study, colorimetric, luminometric and western blot analyses were used to determine the potential of the REE to reduce biomarkers associated with oxidative damage and its potential to enhance the intracellular antioxidant defense system. The REE was found to be hepatoprotective as evidenced by reduced levels of oxidative damage biomarkers (MDA and protein carbonylation) and enhanced antioxidant capacity under glucotoxic conditions as evidenced by elevated GSH (reduced form). We also observed decreased intracellular hydrogen peroxide levels and caspase activity in the REE treated cells and further showed that the REE enhanced SOD2, CAT, and GPx1 protein expression. These effects were dependent on the transcriptional activity of NRF2. Collectively, our results show that the REE enhances the cellular antioxidant defense capacity and may provide a relevant supportive therapeutic option for treating diabetic complications associated with oxidative stress. [ABSTRACT FROM AUTHOR]

This paper reviews provenance, processing and properties of rooibos (Aspalathus linearis, Brum.f) and its numerous biologically active constituents, as well as the currently available knowledge concerning their physiological and medicinal effects and their possible extra‐ and intracellular mechanisms of action. Search for literature was performed in agreement with the preferred reporting items for systematic review criteria in Cochrane Library, PubMed, Web of Science and SCOPUS databases between the years 2000 and 2021. The limited number of in vitro studies suggests an influence of rooibos on basic ovarian cell functions, as well as its potential applicability to control female reproduction and prevent the effect of environmental contaminants on ovarian functions. Nevertheless, further studies are required for better understanding of the character and mechanisms of action, as well as of rooibos' application in reproductive biology and medicine. [ABSTRACT FROM AUTHOR]

Rooibos (Aspalathus linearis) has various health benefits. Two case studies have associated chronic Rooibos consumption with conventional prescription medications, including atorvastatin (ATV), with hepatotoxicity. Statins act by inhibiting hydroxymethylglutaryl‐coenzyme A reductase, a rate‐limiting enzyme in cholesterol synthesis. Although rare, statins are potentially hepatotoxic. The aim was to investigate interactions between aspalathin‐rich Rooibos extract GRT™ and ATV‐induced hepatotoxicity in C3A liver cells cultured with and without palmitate. Effects of co‐treatment of GRT + ATV on cell viability, oxidative stress, apoptosis, mitochondrial integrity, and cellular reactive oxygen species (ROS) production were assessed. Significantly increased ROS production was observed in cells exposed to ATV and palmitate. Combination therapy of GRT + ATV also showed significant increases in ROS production. Under palmitate‐treated conditions, ATV‐induced significant apoptosis which was not ameliorated by GRT + ATV co‐treatment. Despite studies purporting hepatoprotection from Rooibos, our study showed that GRT was unable to modulate ATV‐induced hepatotoxic effects in this model. [ABSTRACT FROM AUTHOR]

Fumonisins are a family of potentially carcinogenic mycotoxins produced by Fusarium verticillioides. Several fumonisins have been identified with fumonisin B1 (FB1) being the most toxic. The canonical mechanism of FB1 toxicity is centered on its structural resemblance with sphinganine and consequent competitive inhibition of ceramide synthase and disruption of lipidomic profiles. Recent and emerging evidence at the molecular level has identified the disruption of mitochondria and excessive generation of toxic reactive oxygen species (ROS) as alternative/additional mechanisms of toxicity. The understanding of how these pathways contribute to FB1 toxicity can lead to the identification of novel, effective approaches to protecting vulnerable populations. Natural compounds with antioxidant properties seem to protect against the induced toxic effects of FB1. Rooibos (Aspalathus linearis), endemic to South Africa, has traditionally been used as a medicinal herbal tea with strong scientific evidence supporting its anecdotal claims. The unique composition of phytochemicals and combination of metabolic activators, adaptogens and antioxidants make rooibos an attractive yet underappreciated intervention for FB1 toxicoses. In the search for a means to address FB1 toxicoses as a food safety problem in developing countries, phytomedicine and traditional knowledge systems must play an integral part. This review aims to summarize the growing body of evidence succinctly, which highlights mitochondrial dysfunction as a secondary toxic effect responsible for the FB1‐induced generation of ROS. We further propose the potential of rooibos to combat this induced toxicity based on its integrated bioactive properties, as a socio‐economically viable strategy to prevent and/or repair cellular damage caused by FB1. Fumonisins are a family of potentially carcinogenic mycotoxins produced by Fusarium verticillioides and its toxicity is most often associated with aberrant sphingolipid metabolism. At the molecular level, the mitochondrial toxicities and generation of toxic reactive oxygen species are emerging as an alternative mechanism of toxicity. The understanding of how these pathways contribute to FB1 toxicity can lead to the identification of novel and economically viable approaches to protecting vulnerable human populations. In this review we summarize the mitochondrial toxicities induced by FB1 and propose the potential of rooibos, a South African herbal tea to combat this toxicity. [ABSTRACT FROM AUTHOR]

Diesel exhaust particles (DEP) are a typical example of air particulate matter generated into the environment from industrial, residential and vehicular diesel engines. Studies have implicated the induction of oxidative stress in the adverse health effect of DEP. In this study, the effect of aqueous rooibos extract (RE) on DEP-induced hepatic oxidative stress was examined and the role of Nrf2-regulation in this effect was evaluated. Wistar rats were divided into 4 groups of 5 rats/group and were administered 0.7 mg/kg DEP subcutaneously and 50 mg/kg RE orally. Group one was given vehicle (saline and DMSO), group two was administered with RE for 4 weeks, group three was given RE for 2 weeks followed by concomitant administration of RE and DEP for further 2 weeks and group four was given DEP twice a week at the last 2 weeks of treatment. Malondialdehyde (MDA), Conjugated dienes (CDs) and GSH levels were determined in the liver homogenate. AST and ALT activities were assayed in the serum and RT-qPCR was used to quantify the gene expression of Nrf2 and HO-1 in the liver. Results showed that RE pre-treatment significantly (p

Objectives: Consumption of high-fat and high-sugar diets in Western countries has increased significantly causing major global health problems including metabolic syndrome and obesity. In addition, studies have suggested that obesity can lead to learning and memory deficits. In this context, the use of natural compounds with low costs, minor side effects and increased antioxidant activity, such as teas, could reduce the damages induced by obesity. We investigated the effect of white, green, red, and black teas (Camellia sinensis) and their possible neuroprotective mechanisms in an experimental obesity model induced by a cafeteria diet (CD). Methods: Female Swiss mice (20–30 g) were used; they received a normal diet or a hypercaloric diet (CD) during 8 weeks. Concomitantly, some mice received orally white, green, red, or black teas (1% dose) or water. Results: The mice subjected to CD showed weight gain, body fat accumulation, increased glucose, cholesterol, and triglycerides, associated to recognition memory deficits and increased reactive species (RS) levels and acetylcholinesterase (AChE) activity in the hippocampus. All teas significantly reduced AChE activity and partially reduced fat accumulation. Green and red teas reduced memory deficit. White, green, and black teas reduced RS levels, while only green and black tea reduced plasma triglyceride levels. Discussion: According to the results obtained it is possible to conclude that green tea was better than other teas in reducing effects of the CD model, being able to protect a greater number of parameters. [ABSTRACT FROM AUTHOR]

Diesel exhaust particles (DEP) are a typical example of air particulate matter generated into the environment from industrial, residential and vehicular diesel engines. Studies have implicated the induction of oxidative stress in the adverse health effect of DEP. In this study, the effect of aqueous rooibos extract (RE) on DEP-induced hepatic oxidative stress was examined and the role of Nrf2-regulation in this effect was evaluated. Wistar rats were divided into 4 groups of 5 rats/group and were administered 0.7 mg/kg DEP subcutaneously and 50 mg/kg RE orally. Group one was given vehicle (saline and DMSO), group two was administered with RE for 4 weeks, group three was given RE for 2 weeks followed by concomitant administration of RE and DEP for further 2 weeks and group four was given DEP twice a week at the last 2 weeks of treatment. Malondialdehyde (MDA), Conjugated dienes (CDs) and GSH levels were determined in the liver homogenate. AST and ALT activities were assayed in the serum and RT-qPCR was used to quantify the gene expression of Nrf2 and HO-1 in the liver. Results showed that RE pre-treatment significantly (p<0.001) decreased DEP-induced elevated serum AST and ALT levels, decreased DEP-induced MDA (p<0.001) and CDs (p<0.05) levels. DEP caused significant (p<0.05) decrease in GSH levels, which was reversed by rooibos extract pre-treatment. DEP also caused significant induction in Nrf2 and HO-1 mRNA levels. However, these inductions were significantly attenuated by RE. In summary, rooibos extract has the potential to protect against DEP-induced oxidative stress in hepatic tissues probably by a mechanism which may not involve activation of the Nrf2-dependent response. [ABSTRACT FROM AUTHOR]

Abstract Aspalathin (ASP) is a C -dihydrochalcone abundantly found in Aspalathus linearis. While we have provide evidence that ASP can protect H9c2 cardiomyoblasts against doxorubicin (Dox)-induced apoptosis through regulation of autophagy, the complete mechanism involved in the cardioprotective effect of this dihydrochalcone remains to be explored. Here we provide evidence that ASP reverses Dox-induced apoptosis through the amelioration of oxidative stress in H9c2 cardiomyoblasts. Cultured cells were treated with 0.2 μM Dox or co-treated with either 20 μM dexrazoxane (Dexra) or 0.2 μM ASP daily for five days, to a final dose of 1 μM Dox, 100 μM Dexra and 1 μM ASP, respectively. Superoxide dismutase, catalase, glutathione, malondialdehyde and dichloro-dihydro-fluorescein diacetate fluorescence were used as end-point measurements for oxidative stress, while JC-1 and TUNEL labeling were performed to assess mitochondria depolarization and apoptosis. Co-treatment with ASP attenuated Dox-induced cardiotoxicity by improving endogenous antioxidant levels and mitochondrial membrane potential, while inhibiting reactive oxygen species production and cellular apoptosis. These findings suggested that ASP can prevent Dox-induced oxidative stress and apoptosis and needs further assessment to confirm its therapeutic potential to prevent Dox-induced cardiotoxicity. Highlights • Aspalathin decreases Doxorubicin-induced oxidative stress. • Aspalathin prevents Doxorubicin-induced cardiotoxicity through amelioration of mitochondria membrane depolarization and cellular apoptosis. • ASP did not decrease the efficacy of Dox to induce apoptosis in Caov-3 cells. [ABSTRACT FROM AUTHOR]

Several medicinal plants are currently used by the food industry as functional additives, for example botanical extracts in herbal drinks. Moreover, the scientific community has recently begun focusing on halophytes as sources of functional beverages. Helichrysum italicum subsp. picardii (everlasting) is an aromatic halophyte common in southern Europe frequently used as spice and in traditional medicine. In this context, this work explored for the first time H. italicum subsp. picardii as a potential source of innovative herbal beverages with potential health promoting properties. For that purpose, infusions and decoctions were prepared from roots, vegetative aerial-organs (stems and leaves) and flowers and evaluated for in vitro antioxidant and anti-diabetic activities. Samples were also assessed for toxicity in different mammalian cell lines and chemically characterized by spectrophotometric methods and ultra-high performance liquid chromatography–photodiode array–mass-spectrometry (UHPLC-PDA-MS). Results were expressed relating to ‘a cup-of-tea’ and compared with those obtained with green tea (Camellia sinensis) and rooibos tisane (Aspalathus linearis). Tisanes from the everlasting’s above-ground organs, particularly flowers, have high polyphenolic content and several phenolics were identified; the main compounds were chlorogenic and quinic acids, dicaffeoylquinic-acid isomers and gnaphaliin-A. The antioxidant activity of beverages from the everlasting’s above-ground organs matched or surpassed that of green tea and rooibos. Its anti-diabetic activity was moderate and toxicity low. Overall, our results suggest that the everlasting is a potential source of innovative and functional herbal beverages. [ABSTRACT FROM AUTHOR]

Green tea from Camellia sinensis plays a neuroprotective role in different neurodegenerative conditions, such as memory deficits in Alzheimer disease (AD). However, whether other teas from Camellia sinensis present similar neuroprotective effect still is not clear. Here we investigate effects of green, red and black tea supplementation on memory and hippocampus oxidative status in a rat model of Alzheimer-like disease (AD-like). Method: Wistar male rats were supplemented with green, red or black tea during 8 weeks before Aβ intra-hippocampal injection (2 μL of Aβ-25–35, CA1 region). AD and sham rats were submitted to memory tests. After euthanasia, oxidative status in the bilateral hippocampus was quantified. Green and red teas avoid memory deficits in AD rats, but only green tea also avoids oxidative stress and damage in the hippocampus. Green tea was more effective for neuroprotection than red and black teas from the Camellia sinensis in the AD rat model. [ABSTRACT FROM AUTHOR]

Memory and cognition impairments resultant of ischemic stroke could be minimized or avoided by antioxidant supplementation. In this regard, the neuroprotective potential of Green tea from Camellia sinensis has been investigated. However, there is a lack of information regarding the neuroprotective potential of others teas processed from the Camellia sinensis . Here we investigate the neuroprotective role of green, red, white and black tea on memory deficits and brain oxidative stress in a model of ischemic stroke in rats. Our findings show that green and red teas prevent deficits in object and social recognition memories, but only green tea protects against deficits in spatial memory and avoids hippocampal oxidative status and intense necrosis and others alterations in the brain tissue. In summary, green tea shows better neuroprotection in ischemic stroke than the others teas from Camellia sinensis . [ABSTRACT FROM AUTHOR]

Background: Indigenous or traditional aqueous plant extracts are commonly used by nearly 80% of the world's population for primary health needs. Accordingly, teas such as Camellia sinensis and herbal teas were characterized for their phytochemical content and potential to offer specific bioactivities that could benefit human health by mitigating oxidative stress and inflammation. Methods: In the present study, we compared the phytochemical profiles, antioxidant, and antiinflammatory activities of four Camellia sinensis teas, including white, green, oolong, black, and two herbal teas such as Rooibos and Yerba mate, which are produced and consumed by different populations worldwide. We also studied the impact of the Rooibos tea on the production of inflammatory mediators, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and different cytokines in Raw 264.7 cells, both with or without interferon γ (IFN-γ) and lipopolysaccharide (LPS) stimulation. Results: White tea had the highest total phenolic content (TPC) and antioxidant activity among the six teas that were examined. In contrast, Rooibos tea had the lowest TPC, antioxidant, and antiinflammatory activities. Yerba mate tea exhibited the greatest potential to inhibit NO production in IFN-γ and LPS-induced Raw 264.7 cells. The anti-inflammatory activity of teas was discovered to be correlated with antioxidant activity and phytochemical composition. Among the six teas examined, only Rooibos tea was found to induce NO in unstimulated Raw 264.7 cells. Under basal conditions, Rooibos tea induced interleukin-1α (IL-1α), IL-1β, IL-6, IL-10, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-α), iNOS, and COX-2 production. However, Rooibos tea also demonstrated a dose-dependent inhibition of IL-6, IL-10, iNOS, and COX-2 expression in stimulated Raw 264.7 cells. Although a high concentration of Rooibos tea was effective in inhibiting induced IL-1α, G-CSF, and GM-CSF, lower concentrations also up-regulated the expression of these cytokines. No inhibitory effects of Rooibos tea examined were discovered with the mitigation of IL-1β and TNF-α. Conclusions: Rooibos tea possesses dual functions on inflammation, either by promoting an inflammatory response to cytokine induction or alternatively inhibiting inflammation during tissue injury or a pathogen infection via a mechanism involving the inhibition of pro-inflammatory cytokines and mediators such as iNOS and COX-2. The potential of Rooibos tea to induce NO production is also noteworthy in mitigating disease states including hypertension and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

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 (2.5 g/kg feed) to male Fischer rats for 28 days, while PECsub, having the highest total polyphenol content and antioxidant activity, was also fed for 90 days. 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 28 days, while serum alkaline phosphatase levels were only significantly ( P < 0.05) increased after 90 days, suggesting alterations in the biliary system. No effect on serum iron levels was noticed after 28 days, but PECsub significantly ( P < 0.05) reduced serum iron after 90 days. Both PECsub and PECgen increased glutathione reductase activity in the liver significantly ( P < 0.05) after 28 days. Reduced glutathione (GSH) content was significantly ( P < 0.05) decreased after 90 days 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 28 days, 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. [ABSTRACT FROM AUTHOR]

Several experimental and animal studies have demonstrated that substances rich in antioxidants can reduce the physicochemical and peroxidative risk factors for calcium oxalate (CaOx) renal stone formation in urine and blood. However, there are very few such investigations in humans. In the present pilot study, two varieties of tea, a green one from Japan (JGT) and a herbal one from South Africa (Rooibos) (RT), both rich in antioxidants, were administered to a group of CaOx stone formers (SF) ( n = 8) for 30 days. Both teas were analysed for polyphenols by high-performance liquid chromatography and for minerals by plasma atomic and optical emission spectroscopy. 24 h urines (baseline and day 30) were analysed for lithogenic factors. CaOx metastable limits and crystal nucleation and growth kinetics were also determined in each urine sample. Deposited crystals were inspected by scanning electron microscopy. Blood samples were collected (baseline and day 30). Biomarkers of oxidative stress including plasma and urinary thiobarbituric acid reactive substances (TBARS) and urinary N-acetyl-β-D-glucosaminidase (NAG) were also determined. Urinary physicochemical risk factors were also investigated after ingestion of RT for 30 days in two control groups (CG1 and CG2), the latter one of which consisted of habitual JGT drinkers. Statistical analyses were performed using Wilcoxon signed rank tests and Mann-Whitney tests for paired and independent measurements, respectively. Several flavonoids and catechins were quantified in RT and JGT, respectively, confirming that both teas are rich sources of antioxidants. Mineral content was found to be far below dietary reference intakes. There were no significant changes in any of the urinary physicochemical or peroxidative risk factors in the control groups or in SF, except for the supersaturation (SS) of brushite (Bru) which decreased in the latter group after ingestion of JGT. Crystal morphology showed a tendency to change from mixed CaOx mono- and di-hydrate to monohydrate after ingestion of each tea. Since the latter form has a stronger binding affinity for epithelial cells, this effect is not protective. Analysis of the physicochemical and peroxidative risk factors in CG1 and CG2 did not reveal any evidence of a synergistic effect between the two teas. Paradoxically, baseline risk factors in the habitual JGT control group were significantly raised relative to those in CG1. Our preliminary results suggest that ingestion of RT and JGT does not reduce the risk factors for CaOx stone formation in humans, but these findings need to be tested in further studies involving much larger sample sizes. [ABSTRACT FROM AUTHOR]

Objective: Previous studies demonstrated that a phenylpropenoic acid glucoside (PPAG) from rooibos (Aspalathus linearis) extract had anti-hyperglycemic activity and significant protective effects on the pancreatic beta cell mass in a chronic diet-induced diabetes model. The present study evaluated the cytoprotective effect of the phytochemical on beta cells exposed to acute cell stress. Methods: Synthetically prepared PPAG was administered orally in mice treated with a single dose of streptozotocin to acutely induce beta cell death and hyperglycemia. Its effect was assessed on beta cell mass, proliferation and apoptotic cell death. Its cytoprotective effect was also studied in vitro on INS-1E beta cells and on human pancreatic islet cells. Results: Treatment with the phytochemical PPAG protected beta cells during the first days after the insult against apoptotic cell death, as evidenced by TUNEL staining, and prevented loss of expression of anti-apoptotic protein BCL2 in vivo. In vitro, PPAG protected INS-1E beta cells from streptozotocin-induced apoptosis and necrosis in a BCL2-dependent and independent way, respectively, depending on glucose concentration. PPAG also protected human pancreatic islet cells against the cytotoxic action of the fatty acid palmitate. Conclusions: These findings show the potential use of PPAG as phytomedicine which protects the beta cell mass exposed to acute diabetogenic stress. [ABSTRACT FROM AUTHOR]

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 756 and 627 mg Gallic acid equivalents (GAE)/kg body weight (bw)/day over 28 and 90 days, respectively, equaling human equivalent doses (HEDs) of 123 and 102 GAE mg/kg bw/day. Aspalathin intake of 295 mg/kg bw/day represents a HED of 48 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. [ABSTRACT FROM AUTHOR]

Exposure to chronic psychological stress may be related to increased reactive oxygen species (ROS) or free radicals, and thus, long-term exposure to high levels of oxidative stress may cause the accumulation of oxidative damage and eventually lead to many neurodegenerative diseases. Compared with other organs, the brain appears especially susceptible to excessive oxidative stress due to its high demand for oxygen. In the case of excessive ROS production, endogenous defense mechanisms against ROS may not be sufficient to suppress ROS-associated oxidative damage. Dietary antioxidants have been shown to protect neurons against a variety of experimental neurodegenerative conditions. In particular, Rooibos tea might be a good source of antioxidants due to its larger proportion of polyphenolic compounds. An optimal animal model for stress should show the features of a stress response and should be able to mimic natural stress progression. However, most animal models of stress, such as cold-restraint, electric foot shock, and burn shock, usually involve physical abuse in addition to the psychological aspects of stress. Animals subjected to chronic restraint or immobilization are widely believed to be a convenient and reliable model to mimic psychological stress. Therefore, in the present study, we propose that immobilization-induced oxidative stress was significantly attenuated by treatment with Rooibos tea. This conclusion is demonstrated by Rooibos tea’s ability to (i) reverse the increase in stress-related metabolites (5-HIAA and FFA), (ii) prevent lipid peroxidation (LPO), (iii) restore stress-induced protein degradation (PD), (iv) regulate glutathione metabolism (GSH and GSH/GSSG ratio), and (v) modulate changes in the activities of antioxidant enzymes (SOD and CAT). [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: 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. Aims of the study: 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. Materials and methods: 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. Results: Plasma antioxidant capacity was not altered, but plasma total polyphenol levels increased significantly after rooibos consumption compared with the control levels (from 79.8±16.9mg/L to 89.8±14.1mg/L). Significant decreases in plasma markers of lipid peroxidation were found after rooibos consumption, as reported by levels of CDs (167.3±29.5nmol/mL vs. 108.8±20.1nmol/mL) and TBARS (1.9±0.6μmol/L vs. 0.9±0.3μmol/L). Reduced glutathione (797±238μmol/L vs. 1082±140μmol/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±1.3mmol/L vs. 3.9±0.7mmol/L) and triacylglycerols (1.7±0.8mmol/L vs. 1.2±0.7mmol/L), while HDL-cholesterol (0.9±0.1mmol/L vs. 1.2±0.2mmol/L) was significantly increased. Conclusion: 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. [Copyright &y& Elsevier]

Abstract: The aim of the study was to assess the effect of drinking rooibos tea (Aspalathus linearis) on total antioxidant capacity (TAC), lipid triacylglycerols, cholesterol and glycaemia plasma levels in humans. In vitro, unfermented rooibos tea displayed a 28% higher value of TRAP than did the fermented beverage. An acute intervention study, cross-over design, was performed, with 15 healthy volunteers who consumed 500ml of either water, unfermented or fermented rooibos teas. Plasma antioxidant capacity increased significantly with both teas, reaching a peak at 1h post-consumption (+6.6%, p <0.05 fermented tea; +2.9%, p <0.01 unfermented tea). No changes in triacylglycerols, cholesterol or uric acid were observed with any of the treatments. A transitory increase in glycaemia at 30min was linked to glucose upload. The data show that rooibos teas represent a source of dietary antioxidants in humans. [Copyright &y& Elsevier]

Background: Rooibos tea is known to be caffeine free with abundant flavonoids. Aspalathin and nothofagin, the main flavonoids contained in Rooibos tea, have stronger anti-oxidative activity than other flavonoids. As oxidative stress can induce inflammation, the anti-inflammatory effects of Rooibos tea were investigated using a rat colitis model. Methods: Seven-week-old Wister rats were divided into two groups: one group given Rooibos tea, and one given water. After four weeks of breeding, serum superoxide dismutase (SOD) levels were determined using the Electron Spin Resonance analysis. Urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations were also determined as reflections of DNA damage using enzyme-linked immunosorbent assay. Furthermore, rats were administrated dextran sodium sulfate (DSS), which is known to induce colitis in rodents, with or without Rooibos tea to evaluate its anti-inflammatory activity. Clinical symptoms, hemoglobin, serum iron and SOD levels were compared between the groups. Results: There were no significant differences in bodyweight gain or laboratory data between the groups. The serum SOD levels were significantly increased, and urine 8-hydroxy-2′-deoxyguanosine levels were significantly decreased in the Rooibos group compared with the controls ( P < 0.05 in each). After DSS administration, the serum SOD levels were significantly higher in the Rooibos group compared to the controls ( P < 0.05). As a result, a decreased hemoglobin level, observed in the control group, was prevented in the Rooibos group after the DSS challenge. Conclusion: Rooibos tea may prevent DNA damage and inflammation by its anti-oxidative activity in vivo. As Rooibos tea is free from caffeine, routine intake may be safe and useful in reducing oxidative stress in children. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of rooibos tea as a natural source of a wide scale of antioxidants on the prevention and treatment of oxidative stress in streptozotocin-induced diabetic rats. Expected significant changes of biochemical parameters characteristic for experimental diabetic state were found in plasma and tissues eight weeks after single dose streptozotocin application Administration of aqueous and alkaline extracts of rooibos tea (or N-acetyl-Lcysteine for comparison) to diabetic rats did not affect markers of the diabetic status (glucose, glycated hemoglobin and fructosamine). Besides the parameters characterizing hepatotoxic effect of streptozotocin, rooibos tea significantly lowered advanced glycation end-products (AGEs) and malondialdehyde (MDA) in the plasma and in different tissues of diabetic rats, particularly MDA concentration in the lens. From these results we can conclude that antioxidant compounds in rooibos tea partially prevent oxidative stress and they are effective in both hydrophobic and hydrophilic biological systems. Therefore, rooibos tea as a commonly used beverage can be recommended as an excellent adjuvant support for the prevention and therapy of diabetic vascular complications, particularly for protecting ocular membrane systems against their peroxidation by reactive oxygen species. [ABSTRACT FROM AUTHOR]

In the pursuit of bioactive phytochemicals as a therapeutic strategy to manage metabolic risk factors for type 2 diabetes (T2D), aspalathin, C-glucosyl dihydrochalcone from rooibos (Aspalathus linearis), has received much attention, along with its C-glucosyl flavone derivatives and phlorizin, the apple O-glucosyl dihydrochalcone well-known for its antidiabetic properties. We provided context for dietary exposure by highlighting dietary sources, compound stability during processing, bioavailability and microbial biotransformation. The review covered the role of these compounds in attenuating insulin resistance and enhancing glucose metabolism, alleviating gut dysbiosis and associated oxidative stress and inflammation, and hyperuricemia associated with T2D, focusing largely on the literature of the past 5 years. A key focus of this review was on emerging targets in the management of T2D, as highlighted in the recent literature, including enhancing of the insulin receptor and insulin receptor substrate 1 signaling via protein tyrosine phosphatase inhibition, increasing glycolysis with suppression of gluconeogenesis by sirtuin modulation, and reducing renal glucose reabsorption via sodium-glucose co-transporter 2. We conclude that biotransformation in the gut is most likely responsible for enhancing therapeutic effects observed for the C-glycosyl parent compounds, including aspalathin, and that these compounds and their derivatives have the potential to regulate multiple factors associated with the development and progression of T2D. [ABSTRACT FROM AUTHOR]

Skin cells suffer continuous damage from chronic exposure to ultraviolet light (UV) that may result in UV-induced oxidative stress and skin thinning. This has necessitated the formulation of cosmeceutical products rich in natural antioxidants and free radical scavengers. Aspalathus linearis (rooibos) is an endemic South African fynbos plant growing naturally in the Western Cape region. The plant is rich in phenolics and other bioactives with a wide spectrum of health benefits. The chemical study of an acetonic extract of green A. linearis afforded a novel compound named linearthin (1) and two known dihydrochalcones, aspalathin (2) and nothofagin (3). The chemical structure of the novel compound was elucidated based on spectroscopic data analysis. The bio-evaluation of the isolated chalcones in vitro for protection against UVB-induced oxidative stress were systematically assessed by examining cell viability, metabolic activity, apoptosis, and cytotoxicity using HaCaT and SK-MEL-1 skin cells models. It was observed that pre-treatment with tested samples for 4- and 24 h at low concentrations were sufficient to protect skin cells from UVB-induced damage in vitro as evidenced by higher cell viability and improved metabolic activity in both keratinocytes (HaCaT) and melanocytes (SK-MEL-1). The results further show that the pre-treatment regimen employed by this study involved some degree of cellular adaptation as evidenced by higher levels of reduced glutathione with a concomitant decrease in lipid peroxidation and lowered caspase 3 activity. Furthermore, compound 1 was most cytoprotective against UVB irradiation of HaCaT cell line (over 24 h) with an IC50 of 282 µg/mL and SK-MEL-1 cell line with IC50 values of 248.3 and 142.6 µg/mL over 4 and 24 h, respectively. On the other hand, HaCaT cells exposed to 2 over 4 h before UVB irradiation showed the highest degree of cytoprotection with an IC50 of 398.9 µg/mL among the four studied samples. These results show that linearthin (1) and the two glycoside dihydrochalcone of A. linearis have the potential to be further developed as antioxidant cosmeceutical ingredients that may protect skin against UVB-induced damage. [ABSTRACT FROM AUTHOR]

While cysteine thiol groups help to maintain the redox status of many proteins, they can be very susceptible to damaging oxidants. Despite broad interest in their antioxidant properties, whether tea polyphenols protect against protein thiol damage of this kind is unclear. This study sought to develop a simple immunoassay for use in screening tea extracts and other antioxidants for thioprotective efficacy at protein thiol groups. Fresh aqueous extracts were prepared from commercially sourced green, white, black and red teas. Traut's reagent (2-iminothiolane) was used to prepare surface-thiolated bovine serum albumin for use as assay substrate in the protein oxidation assay. Oxidative damage was induced during a 15 min incubation with hydrogen peroxide (H 2 O 2) in the presence of tea extracts and reference antioxidants. The substrate protein was then derivatised with dimedone before samples were loaded onto a nitrocellulose membrane housed within a Slot-Blot apparatus. After blocking nonspecific protein binding a commercially available antibody was used to detect dimedone-labelled groups. While the total phenol content of tea extracts typically correlated with their activity in lipid peroxidation and galvinoxyl radical-trapping assays, the former did not fully predict their abilities to suppress H 2 O 2 -induced cysteine oxidation, with black tea extracts displaying greater activity than the other teas and an apparent ability to reverse pre-existing cysteine oxidation. Among the model antioxidants tested, quercetin displayed a heightened ability to suppress cysteine oxidation. This slot-blot immunoassay is a convenient method that facilitates standardised comparisons between the thioprotective properties of structurally- and constitutively-diverse antioxidants. • This paper describes a simple immunoassay that facilitates study of the protective efficacy of antioxidants against peroxide-induced cysteine thiol oxidation. • The method employs surface-thiolated albumin as assay target coupled with the use of dimedone to trap oxidised cysteine groups. • Dimedone-trapped moieties are detected using a commercially available antibody. • The method was useful during screening efforts to evaluate various tea beverages and model antioxidants for thioprotective efficacy. • Black tea and quercetin were identified as having potential thioprotective efficacy. [ABSTRACT FROM AUTHOR]