SUNScholar - Browsing by Author "Joubert, Elizabeth"

Browsing by Author "Joubert, Elizabeth"

Now showing 1 - 20 of 24

Adipose tissue as a possible therapeutic target for polyphenols : a case for Cyclopia extracts as anti-obesity nutraceuticals
(Elsevier, 2019) Jack, Babalwa U.; Malherbe, Christiaan J.; Mamushi, Mokadi Peggy; Muller, Christo J. F.; Joubert, Elizabeth; Louwa, Johan; Pheiffer, Carmen
ENGLISH ABSTRACT: Obesity is a significant contributor to increased morbidity and premature mortality due to increasing the risk of many chronic metabolic diseases such as type 2 diabetes, cardiovascular disease and certain types of cancer. Lifestyle modifications such as energy restriction and increased physical activity are highly effective first-line treatment strategies used in the management of obesity. However, adherence to these behavioral changes is poor, with an increased reliance on synthetic drugs, which unfortunately are plagued by adverse effects. The identification of new and safer anti-obesity agents is thus of significant interest. In recent years, plants and their phenolic constituents have attracted increased attention due to their health-promoting properties. Amongst these, Cyclopia, an endemic South African plant commonly consumed as a herbal tea (honeybush), has been shown to possess modulating properties against oxidative stress, hyperglycemia, and obesity. Likewise, several studies have reported that some of the major phenolic compounds present in Cyclopia spp. exhibit anti-obesity effects, particularly by targeting adipose tissue. These phenolic compounds belong to the xanthone, flavonoid and benzophenone classes. The aim of this review is to assess the potential of Cyclopia extracts as an anti-obesity nutraceutical as underpinned by in vitro and in vivo studies and the underlying cellular mechanisms and biological pathways regulated by their phenolic compounds.
Anti-inflammatory effects of Aspalathus linearis and Cyclopia spp. extracts in a UVB/keratinocyte (HaCaT) model utilising interleukin-1α accumulation as biomarker
(MDPI, 2016-10-02) Magcwebeba, Tandeka; Swart, Pieter; Swanevelder, Sonja; Joubert, Elizabeth; Gelderblom, Wentzel
Ultraviolet B (UVB) radiation is one of the major predisposing risk factors of skin cancer. The anticancer and photoprotective effects of unoxidized rooibos (Aspalathus linearis) and honeybush (Cyclopia) herbal teas, containing high levels of dihydrochalones and xanthones, respectively, have been demonstrated in skin cancer models in vivo. In the current study, the anti-inflammatory effects of methanol and aqueous extracts of these herbal teas were investigated in a UVB/HaCaT keratinocyte model with intracellular interleukin-1α (icIL-1α) accumulation as a biomarker. Extracts of green tea (Camellia sinensis) served as benchmark. Both extracts of green tea and rooibos, as well as the aqueous extract of C. intermedia, enhanced UVB-induced inhibition of cell viability, proliferation and induction of apoptosis, facilitating the removal of icIL-1α. The underlying mechanisms may involve mitochondrial dysfunction exhibiting pro-oxidant responses via polyphenol-iron interactions. The methanol extracts of honeybush, however, protected against UVB-induced reduction of cell growth parameters, presumably via antioxidant mechanisms that prevented the removal of highly inflamed icIL-1α-containing keratinocytes via apoptosis. The dual antioxidant and/or pro-oxidant role of the polyphenolic herbal tea constituents should be considered in developing preventive strategies against UVB-induced skin carcinogenesis. The indirect removal of UVB damaged keratinocytes by herbal tea extracts via apoptosis may find application in the prevention of photo-induced inflammation.
Aspalathin protects the heart against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression
(MDPI, 2017) Dludla, Phiwayinkosi V.; Muller, Christo J. F.; Joubert, Elizabeth; Louw, Johan; Essop, M. Faadiel; Gabuza, Kwazi B.; Ghoor, Samira; Huisamen, Barbara; Johnson, Rabia
Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress, and apoptosis. The protective mechanism of ASP remains unknown. However, as one of possible, it is well known that phytochemical flavonoids reduce oxidative stress via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation resulting in up-regulation of antioxidant genes and enzymes. Therefore, we hypothesized that ASP protects the myocardium against HG- and hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice, respectively. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for six weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for six weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced oxidative stress through activation of Nrf2 and its downstream target genes.
Aspalathin, a natural product with the potential to reverse hepatic insulin resistance by improving energy metabolism and mitochondrial respiration
(Public Library of Science, 2019) Mazibuko-Mbeje, Sithandiwe E.; Dludla, Phiwayinkosi V.; Johnson, Rabia; Joubert, Elizabeth; Louw, Johan; Ziqubu, Khanyisani; Tiano, Luca; Silvestri, Sonia; Orlando, Patrick; Opoku, Andy R.; Muller, Christo J. F.
ENGLISH ABSTRACT: Aspalathin is a rooibos flavonoid with established blood glucose lowering properties, however, its efficacy to moderate complications associated with hepatic insulin resistance is unknown. To study such effects, C3A liver cells exposed to palmitate were used as a model of hepatic insulin resistance. These hepatocytes displayed impaired substrate metabolism, including reduced glucose transport and free fatty acid uptake. These defects included impaired insulin signaling, evident through reduced phosphatidylinositol-4,5-bisphosphate 3-kinase/ protein kinase B (PI3K/AKT) protein expression, and mitochondrial dysfunction, depicted by a lower mitochondrial respiration rate. Aspalathin was able to ameliorate these defects by correcting altered substrate metabolism, improving insulin signaling and mitochondrial bioenergetics. Activation of 5´-adenosine monophosphate-activated protein kinase (AMPK) may be a plausible mechanism by which aspalathin increases hepatic energy expenditure. Overall, these results encourage further studies assessing the potential use of aspalathin as a nutraceutical to improve hepatocellular energy expenditure, and reverse metabolic disease-associated complications.
Aspalathin-enriched green rooibos extract reduces hepatic insulin resistance by modulating PI3K/AKT and AMPK pathways
(MDPI, 2019-02-01) Mazibuko-Mbeje, Sithandiwe E.; Dludla, Phiwayinkosi V.; Roux, Candice; Johnson, Rabia; Ghoor, Samira; Joubert, Elizabeth; Louw, Johan
We previously demonstrated that an aspalathin-enriched green rooibos extract (GRE) reversed palmitate-induced insulin resistance in C2C12 skeletal muscle and 3T3-L1 fat cells by modulating key effectors of insulin signalling such as phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK). However, the effect of GRE on hepatic insulin resistance is unknown. The effects of GRE on lipid-induced hepatic insulin resistance using palmitate-exposed C3A liver cells and obese insulin resistant (OBIR) rats were explored. GRE attenuated the palmitate-induced impairment of glucose and lipid metabolism in treated C3A cells and improved insulin sensitivity in OBIR rats. Mechanistically, GRE treatment significantly increased PI3K/AKT and AMPK phosphorylation while concurrently enhancing glucose transporter 2 expression. These findings were further supported by marked stimulation of genes involved in glucose metabolism, such as insulin receptor (Insr) and insulin receptor substrate 1 and 2 (Irs1 and Irs2), as well as those involved in lipid metabolism, including Forkhead box protein O1 (FOXO1) and carnitine palmitoyl transferase 1 (CPT1) following GRE treatment. GRE showed a strong potential to ameliorate hepatic insulin resistance by improving insulin sensitivity through the regulation of PI3K/AKT, FOXO1 and AMPK-mediated pathways.
Aspalathin-rich green rooibos extract lowers LDL-cholesterol and oxidative status in high-fat diet-induced diabetic vervet monkeys
(2019-05-02) Orlando, Patrick; Chellan, Nireshni; Louw, Johan; Tiano, Luca; Cirilli, Ilenia; Dludla, Phiwayinkosi; Joubert, Elizabeth; Muller, Christo J. F.
Type 2 diabetic patients possess a two to four-fold-increased risk for cardiovascular diseases (CVD). Hyperglycemia, oxidative stress associated with endothelial dysfunction and dyslipidemia are regarded as pro-atherogenic mechanisms of CVD. In this study, high-fat diet-induced diabetic and non-diabetic vervet monkeys were treated with 90 mg/kg of aspalathin-rich green rooibos extract (Afriplex GRT) for 28 days, followed by a 1-month wash-out period. Supplementation showed improvements in both the intravenous glucose tolerance test (IVGTT) glycemic area under curve (AUC) and total cholesterol (due to a decrease of the low-density lipoprotein [LDL]) values in diabetics, while non-diabetic monkeys benefited from an increase in high-density lipoprotein (HDL) levels. No variation of plasma coenzyme Q10 (CoQ10) were found, suggesting that the LDL-lowering effect of Afriplex GRT could be related to its ability to modulate the mevalonate pathway differently from statins. Concerning the plasma oxidative status, a decrease in percentage of oxidized CoQ10 and circulating oxidized LDL (ox-LDL) levels after supplementation was observed in diabetics. Finally, the direct correlation between the amount of oxidized LDL and total LDL concentration, and the inverse correlation between ox-LDL and plasma CoQ10 levels, detected in the diabetic monkeys highlighted the potential cardiovascular protective role of green rooibos extract. Taken together, these findings suggest that Afriplex GRT could counteract hyperglycemia, oxidative stress and dyslipidemia, thereby lowering fundamental cardiovascular risk factors associated with diabetes.
Characterization of volatiles and aroma-active compounds in honeybush (Cyclopia subternata) by GC-MS and GC-O analysis
(American Chemical Society, 2012-03) Le Roux, Maritha.; Cronje, J. Christel; Burger, B. V.; Joubert, Elizabeth
Volatile organic compounds (VOCs) in fermented honeybush, Cyclopia subternata, were sampled by means of a high-capacity headspace sample enrichment probe (SEP) and analyzed by gas chromatography-mass spectrometry (GC-MS). Stereochemistry was determined by means of enantioselective GC-MS with derivatized β-cyclodextrin columns as chiral selectors. A total of 183 compounds, the majority of which are terpenoids (103; 56%), were identified by comparing their mass spectra and retention indices with those of reference compounds or tentatively identified by comparison with spectral library or literature data. Of these compounds, 37 were determined by gas chromatography-olfactometry (GC-O), using detection frequency (DF) and aroma extract dilution analysis (AEDA), to be odor-active (FD ≥ 2). (E)-β-Damascenone, (R/S)-linalool, (E)-β-damascone, geraniol, (E)-β-ionone, and (7E)-megastigma-5,7,9-trien-4-one were identified with the highest FD factors (≥512). The odors of certain compounds, that is, (6E,8Z)-megastigma-4,6,8-trien-3-one, (6E,8E)-megastigma-4,6,8-trien-3-one, (7E)-megastigma-5,7,9-trien-4-one, 10-epi-γ-eudesmol, epi-α- muurolol, and epi-α-cadinol, were perceived by GC-O assessors as typically honeybush-like. © 2012 American Chemical Society.
Comprehensive phenolic profiling of Cyclopia genistoides (L.) Vent. by LC-DAD-MS and -MS/MS reveals novel xanthone and benzophenone constituents
(MDPI, 2014-08) Beelders, Theresa; De Beer, Dalene; Stander, Maria A.; Joubert, Elizabeth
A high-performance liquid chromatographic (HPLC) method coupled with diode-array detection (DAD) was optimized for the qualitative analysis of aqueous extracts of Cyclopia genistoides. Comprehensive insight into the phenolic profile of unfermented and fermented sample extracts was achieved with the identification of ten compounds based on comparison with authentic reference standards and the tentative identification of 30 additional compounds by means of electrospray ionization mass spectrometry (ESI-MS) and tandem MS detection. Three iriflophenone-di-O,C-hexoside isomers, three xanthone-dihydrochalcone derivatives and one dihydrochalcone are herein tentatively identified for the first time in C. genistoides. Of special interest is one iriflophenone-di-O,C-hexoside present in large amounts. New compounds (tentatively) identified for the first time in this species, and also in the genus Cyclopia, include two aromatic amino acids, one flavone, an iriflophenone-di-C-hexoside, a maclurin-di-O,C-hexoside, two tetrahydroxyxanthone-C-hexoside isomers, a tetrahydroxyxanthone-di-O,C-hexoside, two symmetric tetrahydroxyxanthone-C-hexoside dimers, nine glycosylated flavanone derivatives and five glycosylated phenolic acid derivatives. The presence of new compound subclasses in Cyclopia, namely aromatic amino acids and glycosylated phenolic acids, was demonstrated. The HPLC-DAD method was successfully validated and applied to the quantitative analysis of the paired sample extracts. In-depth analysis of the chemical composition of C. genistoides hot water extracts gave a better understanding of the chemistry of this species that will guide further research into its medicinal properties and potential uses.
Differential modulation of gene expression encoding hepatic and renal xenobiotic metabolizing enzymes by an aspalathin-enriched rooibos extract and aspalathin
(Thieme Gruppe, 2019) Abrahams, Sameega; Samodien, Sedicka; Lilly, Mariska; Joubert, Elizabeth; Gelderblom, Wentzel
Modulation of the expression of hepatic and renal genes encoding xenobiotic metabolizing enzymes by an aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was investigated in the liver and kidneys of F344 rats following dietary exposure of 28 d, as well as selected xenobiotic metabolizing genes in rat primary hepatocytes. In the liver, GRE upregulated genes (p < 0.05) encoding aldehyde dehydrogenase, glucose phosphate isomerase, and cytochrome P450 while 17β-hydroxysteroid dehydrogenase 2 (Hsd17β2) was downregulated. In primary hepatocytes, GRE lacked any effect, while aspalathin downregulated Hsd17β2, mimicking the effect of GRE in vivo, and upregulated catechol-O-methyl transferase and marginally (p < 0.1) cytochrome P450 2e1. In the kidneys, GRE upregulated (p < 0.05) genes encoding the phase II xenobiotic metabolism enzymes, glutathione-S-transferase mµ and microsomal glutathione-S-transferase, while downregulating genes encoding the ATP binding cassette transporter, cytochrome P450, gamma glutamyltransferase 1, and N-acetyltransferase 1. Differential modulation of the expression of xenobiotic metabolizing genes in vivo and in vitro by GRE is dose-related, duration of exposure, the tissue type, and interactions between specific polyphenol and/or combinations thereof. Aspalathin is likely to be responsible for the downregulation of estradiol and testosterone catabolism by GRE in the liver. The differential gene expression by GRE in the liver and kidneys could, depending on the duration exposure and dose utilized, determine the safe use of such an extract in humans for specific health and/or disease outcomes.
Evaluation of the phytoestrogenic activity of Cyclopia genistoides (honeybush) methanol extracts and relevant polyphenols
(American Chemical Society, 2007-04) Verhoog, Nicolette J. D.; Joubert, Elizabeth; Louw, Ann
Unfermented C. genistoides methanol extracts of different harvestings and selected polyphenols were evaluated for phytoestrogenic activity by comparing binding to both ER subtypes, transactivation of an ERE-containing promoter reporter, proliferation of MCF-7-BUS and MDA-MB-231 breast cancer cells, and binding to SHBG. The extracts from one harvesting of C. genistoides (P104) bound to both ER subtypes. All extracts transactivated ERE-containing promoter reporters via ERβ but not via ERα. All extracts, except P122, caused proliferation of the estrogen-sensitive MCF-7-BUS cells. Proliferation of MCF-7-BUS cells was ER-dependent as ICI 182,780 reversed proliferation. Physiologically more relevant, extracts antagonized E2-induced MCF-7-BUS cell proliferation. Furthermore, all extracts, except P122, induced proliferation of the estrogen-insensitive MDA-MB-231 cells, suggesting that the extracts are able to induce ER-dependent and ER-independent cell proliferation. Binding to SHBG by extracts was also demonstrated. These results clearly show that C. genistoides methanol extracts display phytoestrogenic activity and act predominantly via ERβ. HPLC and LC-MS analysis, however, suggests that the observed phytoestrogenic activity cannot be ascribed to polyphenols known to be present in other Cyclopia species. © 2007 American Chemical Society.
Food ingredient extracts of Cyclopia subternata (Honeybush) : variation in phenolic composition and antioxidant capacity
(MDPI, 2012) De Beer, Dalene; Schulze, Alexandra E.; Joubert, Elizabeth; De Villiers, Andre; Malherbe, Christiaan J.; Stander, Maria A.
Cyclopia subternata plants are traditionally used for the production of the South African herbal tea, honeybush, and recently as aqueous extracts for the food industry. A C. subternata aqueous extract and mangiferin (a major constituent) are known to have anti-diabetic properties. Variation in phenolic composition and antioxidant capacity is expected due to cultivation largely from seedlings, having implications for extract standardization and quality control. Aqueous extracts from 64 seedlings of the same age, cultivated under the same environmental conditions, were analyzed for individual compound content, total polyphenol (TP) content and total antioxidant capacity (TAC) in a number of assays. An HPLC method was developed and validated to allow quantification of xanthones (mangiferin, isomangiferin), flavanones (hesperidin, eriocitrin), a flavone (scolymoside), a benzophenone (iriflophenone-3-C-β-glucoside) and dihydrochalcones (phloretin-3',5'-di-C-β-glucoside, 3-hydroxyphloretin-3',5'-di-C-hexoside). Additional compounds were tentatively identified using mass spectrometric detection, with the presence of the 3-hydroxyphloretin-glycoside, an iriflophenone-di-O,C-hexoside, an eriodictyol-di-C-hexoside and vicenin-2 being demonstrated for the first time. Variability of the individual phenolic compound contents was generally higher than that of the TP content and TAC values. Among the phenolic compounds, scolymoside, hesperidin and iriflophenone-3-C-β-glucoside contents were the most variable. A combination of the measured parameters could be useful in product standardization by providing a basis for specifying minimum levels.
Hyperglycemia-induced oxidative stress and heart disease-cardioprotective effects of rooibos flavonoids and phenylpyruvic acid-2-O-β-D-glucoside
(BMC (part of Springer Nature), 2017) Dludla, Phiwayinkosi V.; Joubert, Elizabeth; Muller, Christo J. F.; Louw, Johan; Johnson, Rabia
Diabetic patients are at an increased risk of developing heart failure when compared to their non-diabetic counter parts. Accumulative evidence suggests chronic hyperglycemia to be central in the development of myocardial infarction in these patients. At present, there are limited therapies aimed at specifically protecting the diabetic heart at risk from hyperglycemia-induced injury. Oxidative stress, through over production of free radical species, has been hypothesized to alter mitochondrial function and abnormally augment the activity of the NADPH oxidase enzyme system resulting in accelerated myocardial injury within a diabetic state. This has led to a dramatic increase in the exploration of plant-derived materials known to possess antioxidative properties. Several edible plants contain various natural constituents, including polyphenols that may counteract oxidative-induced tissue damage through their modulatory effects of intracellular signaling pathways. Rooibos, an indigenous South African plant, well-known for its use as herbal tea, is increasingly studied for its metabolic benefits. Prospective studies linking diet rich in polyphenols from rooibos to reduced diabetes associated cardiovascular complications have not been extensively assessed. Aspalathin, a flavonoid, and phenylpyruvic acid-2-O-β-D-glucoside, a phenolic precursor, are some of the major compounds found in rooibos that can ameliorate hyperglycemia-induced cardiomyocyte damage in vitro. While the latter has demonstrated potential to protect against cell apoptosis, the proposed mechanism of action of aspalathin is linked to its capacity to enhance the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression, an intracellular antioxidant response element. Thus, here we review literature on the potential cardioprotective properties of flavonoids and a phenylpropenoic acid found in rooibos against diabetes-induced oxidative injury.
Impact of cold versus hot brewing on the phenolic profile and antioxidant capacity of rooibos (Aspalathus linearis) herbal tea
(MDPI, 2019-10-21) Damiani, Elisabetta; Carloni, Patricia; Rocchetti, Gabriele; Senizza, Biancamaria; Tiano, Luca; Joubert, Elizabeth; de Beer, Dalene; Lucini, Luigi
Consumption of rooibos (Aspalathus linearis) as herbal tea is growing in popularity worldwide and its health-promoting attributes are mainly ascribed to its phenolic composition, which may be affected by the brewing conditions used. An aspect so far overlooked is the impact of cold brewing vs regular brewing and microwave boiling on the (poly) phenolic profile and in vitro antioxidant capacity of infusions prepared from red (‘fermented’, oxidized) and green (‘unfermented’, unoxidized) rooibos, the purpose of the present study. By using an untargeted metabolomics-based approach (UHPLC-QTOF mass spectrometry), 187 phenolic compounds were putatively annotated in both rooibos types, with flavonoids, tyrosols, and phenolic acids the most represented type of phenolic classes. Multivariate statistics (OPLS-DA) highlighted the phenolic classes most affected by the brewing conditions. Similar antioxidant capacities (ORAC and ABTS assays) were observed between cold- and regular-brewed green rooibos and boiled-brewed red rooibos. However, boiling green and red rooibos delivered infusions with the highest antioxidant capacities and total polyphenol content. The polyphenol content strongly correlated with the in vitro antioxidant capacities, especially for flavonoids and phenolic acids. These results contribute to a better understanding of the impact of the preparation method on the potential health benefits of rooibos tea.
In vitro a-glucosidase inhibition by honeybush (Cyclopia genistoides) food ingredient extract-potential for dose reduction of acarbose through synergism
(Royal Society of Chemistry, 2020-06-29) Miller, Neil; Malherbe, Christiaan J.; Joubert, Elizabeth
Extracts of Cyclopia species are used as food ingredients. In vitro α-glucosidase (AG) inhibition by ultrafiltered C. genistoides extract, fractions enriched in xanthones (XEF) and benzophenones (BEF), as well as mangiferin, isomangiferin, 3-β-D-glucopyranosyliriflophenone (I3G) and 3-β-D-glucopyranosyl-4-O-β-D-glucopyranosyliriflophenone (IDG) was determined with acarbose as positive control. XEF was more potent than the extract and BEF (IC50 = 43.3, 95.5 and 205.7 μg mL−1, respectively). Compounds demonstrated potency in the descending order: acarbose (IC50 = 44.3 μM) > mangiferin (102.2 μM) > isomangiferin (119.8 μM) > I3G (237.5 μM) > IDG (299.4 μM). The combination index (CI) was used to determine synergism (CI < 0.7) as demonstrated for combinations of acarbose with XEF, BEF or the respective compounds at 50% and 75% effect levels. The greatest potential acarbose dose reductions (>six-fold) across all effect levels were calculated for combinations of acarbose with mangiferin or isomangiferin, explaining the greater acarbose dose reduction potential of XEF vs. BEF. The effect of batch-to-batch variation (n = 10) of raw plant material on AG inhibition was quantified at a fixed concentration (160 μg mL−1). XEFs (xanthone content = 223–481 g kg−1) achieved AG inhibition of 63–72%, whereas BEFs (benzophenone content = 114–251 g kg−1) achieved AG inhibition of 26–34%, with weak linear correlation (R2 < 0.43) between target compound content of the fractions and their achieved AG inhibition. Thus, extract fractions of C. genistoides, enriched in xanthones and benzophenones, show potential in reducing the effective dose of acarbose required to prevent postprandial hyperglycaemia.
In vitro chemopreventive properties of green tea, rooibos and honeybush extracts in skin cells
(MDPI, 2016-11-25) Magcwebeba, Tandeka U.; Swart, Pieter; Swanevelder, Sonja; Joubert, Elizabeth; Gelderblom, Wentzel C. A.
The chemopreventive properties of the herbal teas rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) have been demonstrated on mouse skin in vivo but the underlying mechanisms are not clear. The aim of the current study was to determine the anti-proliferative and pro-apoptotic activity of methanol and aqueous extracts of rooibos and two Cyclopia species in different skin cells, using green tea (Camellia sinensis) as a benchmark. Extracts were also characterised for their major individual polyphenols by high performance liquid chromatography and spectroscopically for the total polyphenol (TP) groups. The methanol extract of rooibos, containing higher levels of polyphenols than its aqueous extract, displayed similar activity to green tea as it selectively targeted premalignant cells by inhibiting cell proliferation at lower concentrations whilst inducing apoptosis via membrane depolarisation at higher concentrations. Specific roles of the major rooibos dihydrochalcones and flavanol/proanthocyanidin-type (FLAVA) compounds are likely to be involved. The aqueous extracts of the Cyclopia species were more active against cell proliferation and at inducing apoptosis which was associated with a higher FLAVA content and a reduced TP/FLAVA ratio. In contrast, their methanol extracts exhibited a cytoprotective effect against apoptosis which was related to their monomeric xanthone and flavanone content. The underlying chemopreventive properties of green tea and the herbal teas appear to be associated with diverse and complex monomeric/polymeric polyphenolic cell interactions.
Inhibitory interactions of Aspalathus linearis (Rooibos) extracts and compounds, aspalathin and Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid, on cytochromes metabolizing hypoglycemic and hypolipidemic drugs
(MDPI, 2016-11-12) Patel, Oelfah; Muller, Christo; Joubert, Elizabeth; Louw, Johan; Rosenkranz, Bernd; Awortwe, Charles
Rooibos extract, due to its glucose and lipid lowering effects, has potential as a nutraceutical for improvement of metabolic dysfunction. Potential herb-drug interactions as a result of the use of natural products are of increasing concern. Cytochrome P450 enzymes, CYP2C8, CYP2C9, and CYP3A4, are important in the metabolism of hypoglycemic drugs, such as thiazolidinediones (TZDs) and sulfonylureas, and hypocholesterolemic drugs, such as atorvastatin. This study investigated the effects of rooibos extracts, prepared from “unfermented” and “fermented” rooibos plant material and two of the major bioactive compounds, Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG) and aspalathin (ASP), on Vivid® recombinant CYP450 enzymes. Unfermented (GRT) and fermented (FRE) rooibos extracts inhibited the activity of CYP2C8 (7.69 ± 8.85 µg/mL and 8.93 ± 8.88 µg/mL, respectively) and CYP3A4 (31.33 ± 4.69 µg/mL and 51.44 ± 4.31 µg/mL, respectively) based on their respective IC50 concentrations. Both extracts dose- and time-dependently inhibited CYP2C8 activity, but only time-dependently inhibited CYP2C9. CYP3A4 showed concentration-dependent inhibition by ASP, GRT, and FRE at 25, 50, and 100 µg/mL concentrations. ASP, GRT, and FRE time-dependently inhibited CYP3A4 activity with GRT and FRE showing a more potent time-dependent inhibition, comparable to erythromycin. These findings suggest that herb-drug interactions may occur when nutraceuticals containing rooibos extracts are co-administered with hypoglycemic drugs such as TZDs, sulfonylureas, and dyslipidemic drug, atorvastatin.
Intestinal transport characteristics and metabolism of C-glucosyl dihydrochalcone, aspalathin
(MDPI, 2017) Bowles, Sandra; Joubert, Elizabeth; De Beer, Dalene; Louw, Johan; Brunschwig, Christel; Njoroge, Mathew; Lawrence, Nina; Wiesner, Lubbe; Chibale, Kelly; Muller, Christo
Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1–150 µM had an apparent rate of permeability (Papp) typical of poorly absorbed compounds (1.73 × 10⁻⁶cm/s). Major glucose transporters, sodium glucose linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), and efflux protein (P-glycoprotein, PgP) (1.84 × 10⁻⁶ cm/s; efflux ratio: 1.1) were excluded as primary transporters, since the Papp of aspalathin was not affected by the presence of specific inhibitors. The Papp of aspalathin was also not affected by constituents of aspalathin-enriched rooibos extracts, but was affected by high glucose concentration (20.5 mM), which decreased the Papp value to 2.9 × 10⁻⁷ cm/s. Aspalathin metabolites (sulphated, glucuronidated and methylated) were found in mouse urine, but not in blood, following an oral dose of 50 mg/kg body weight of the pure compound. Sulphates were the predominant metabolites. These findings suggest that aspalathin is absorbed and metabolised in mice to mostly sulphate conjugates detected in urine. Mechanistically, we showed that aspalathin is not actively transported by the glucose transporters, but presumably passes the monolayer paracellularly.
Model development for predicting in vitro bio-capacity of green rooibos extract based on composition for application as screening tool in quality control
(Royal Society of Chemistry, 2020-03-09) Viraragavan, Amsha; Hlengwa, Nokulunga; De Beer, Dalene; Riedel, Sylvia; Miller, Neil; Bowles, Sandra; Walczak, Beata; Muller, Christo; Joubert, Elizabeth
Mounting evidence of the ability of aspalathin to target underlying metabolic dysfunction relevant to the development or progression of obesity and type 2 diabetes created a market for green rooibos extract as a functional food ingredient. Aspalathin is the obvious choice as a chemical marker for extract standardisation and quality control, however, often the concentration of a single constituent of a complex mixture such as a plant extract is not directly related to its bio-capacity, i.e. the level of in vitro bioactivity effected in a cell system at a fixed concentration. Three solvents (hot water and two EtOH–water mixtures), previously shown to produce bioactive green rooibos extracts, were selected for extraction of different batches of rooibos plant material (n = 10). Bio-capacity of the extracts, tested at 10 μg ml−1, was evaluated in terms of glucose uptake by C2C12 and C3A cells and lipid accumulation in 3T3-L1 cells. The different solvents and inter-batch plant variation delivered extracts ranging in aspalathin content from 54.1 to 213.8 g kg−1. The extracts were further characterised in terms of other major flavonoids (n = 10) and an enolic phenylpyruvic acid glucoside, using HPLC-DAD. The 80% EtOH–water extracts, with the highest mean aspalathin content (170.9 g kg−1), had the highest mean bio-capacity in the respective assays. Despite this, no significant (P ≥ 0.05) correlation existed between aspalathin content and bio-capacity, while the orientin, isoorientin and vitexin content correlated moderately (r ≥ 0.487; P < 0.05) with increased glucose uptake by C2C12 cells. Various multivariate analysis methods were then applied with Evolution Program-Partial Least Squares (EP-PLS) resulting in models with the best predictive power. These EP-PLS models, based on all quantified compounds, predicted the bio-capacity of the extracts for the respective cell types with RMSECV values ≤ 11.5, confirming that a complement of compounds, and not aspalathin content alone, is needed to predict the in vitro bio-capacity of green rooibos extracts. Additionally, the composition of hot water infusions of different production batches of green rooibos (n = 29) at ‘cup-of-tea’ equivalence was determined to relate dietary supplementation with the extract to intake in the form of herbal tea.
Nutraceutical value of yellow- and red-fleshed South African plums (prunus salicina lindl.) : evaluation of total antioxidant capacity and phenolic composition
(MDPI, 2014) Venter, Alet; Joubert, Elizabeth; De Beer, Dalene
Ten South African plum cultivars and selections, including yellow- and redfleshed plums from two harvest seasons were evaluated in terms of nutraceutical value (phenolic composition, total polyphenol content (TPC) and total antioxidant capacity (TAC)) and fruit attributes (colour, fruit mass, etc.). Plums were evaluated at two maturity stages, i.e., directly after harvest (unripe) and after a commercial cold storage and ripening regime (ripe). The phenolic composition of South African plums varied greatly, both qualitatively and quantitatively, between cultivars and selections. Neochlorogenic acid, cyanidin-3-O-glucoside and quercetin-3-O-glucoside were the predominant hydroxycinnamic acid, anthocyanin and flavonol, respectively, although not present in all plums. The flavan-3-ols, (+)-catechin, (−)-epicatechin and procyanidins B1 and B2, were present in all plums. Red-fleshed plums tended to display higher TAC and TPC than yellow-fleshed plums. The flavan-3-ol content was highly correlated with TAC. The effect of harvest season was cultivar-dependent, but cultivar differences were not obscured. In terms of maturity stage, the ripe fruits tended to contain higher levels of anthocyanins and some flavonol compounds, although the TPC and TAC were not affected in most cases. South African plums, especially the red-fleshed selections PR04-32 and PR04-35, were shown to provide generally high TAC and TPC compared to literature values.
Phytoestrogenic potential of Cyclopia extracts and polyphenols
(Georg Thieme Verlag, 2013-05) Louw, Ann; Joubert, Elizabeth; Visser, Koch
Cyclopia Vent. species, commonly known as honeybush, are endemic to Southern Africa. The plant is traditionally used as an herbal tea but several health benefits have recently been recorded. This minireview presents an overview of polyphenols found in Cyclopia and focusses on the phytoestrogenic potential of selected polyphenols and of extracts prepared from the plant.

Browsing by Author "Joubert, Elizabeth"

Results Per Page

Sort Options