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1.
Food Chem ; 351: 129273, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33662907

RESUMO

Heat processing of ready-to-drink beverages is required to ensure a microbiologically safe product, however, this can result in the loss of bioactive compounds responsible for functionality. The objective of this study was to establish the thermal stability of a novel dihydrochalcone, 3',5'-di-ß-d-glucopyranosyl-3-hydroxyphloretin (2), 3',5'-di-ß-d-glucopyranosylphloretin (3) and other Cyclopia subternata phenolic compounds, in model solutions with or without citric acid and ascorbic acid. The solutions were heated at 93, 121 and 135 °C, relevant to pasteurisation, commercial sterilisation and ultra-high temperature (UHT) pasteurisation, respectively. For most compounds, the acids decreased the second order reaction rate constants, up to 27 times. Compound 2 (46.29 ± 0.53 (g/100 g)-1 h-1), and to a lesser extent compound 3 (5.94 ± 0.01 (g/100 g)-1 h-1) were the most thermo-unstable compounds when treated at 135 °C without added acids. Even though differential effects were observed for compounds at different temperatures and formulations, overall, the phenolic compounds were most stable under UHT pasteurisation conditions.


Assuntos
Bebidas/análise , Chalconas/química , Fabaceae/química , Extratos Vegetais/química , Polifenóis/química , Temperatura , Glicosilação , Pasteurização , Fenóis/análise , Soluções
2.
Planta Med ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33142345

RESUMO

Fractions of an ultrafiltered Cyclopia genistoides extract, respectively enriched in xanthones and benzophenones, were previously shown to inhibit mammalian α-glucosidase in vitro. The present study investigated ex vivo intestinal transport of these fractions, using excised porcine jejunal tissue, to determine whether the gut could be a predominant in vivo site of action. The major bioactive compounds, the xanthones (mangiferin, isomangiferin) and benzophenones (3-ß-D-glucopyranosyliriflophenone, 3-ß-D-glucopyranosyl-4-O-ß-D-glucopyranosyliriflophenone) exhibited poor permeation in the absorptive direction with a relatively high efflux ratio (efflux ratio > 1). The efflux ratio of 3-ß-D-glucopyranosyl-4-O-ß-D-glucopyranosyliriflophenone (3.05) was similar to rhodamine 123 (2.99), a known substrate of intestinal P-glycoprotein 1 efflux transporters. Low epithelial membrane transport rates, coupled with efflux mechanisms, would effectively concentrate these bioactive compounds at the target site (gut lumen). Storage stability testing and moisture sorption assays of the xanthone-enriched fraction, benzophenone-enriched fraction, and ultrafiltered Cyclopia genistoides extract were performed to determine their susceptibility to physical and chemical degradation during storage. Hygroscopicity of the powders, indicated by moisture uptake, decreased in the order: benzophenone-enriched fraction (22.7%) > ultrafiltered Cyclopia genistoides extract (14.0%) > xanthone-enriched fraction (10.7%). 3-ß-D-Glucopyranosylmaclurin, a minor benzophenone, was the least stable of the compounds, degrading faster in the benzophenone-enriched fraction than in ultrafiltered Cyclopia genistoides extract, suggesting that the ultrafiltered extract matrix may provide a degree of protection against chemical degradation. Compound degradation during 12 wk of storage at 40 °C in moisture-impermeable containers was best explained by first order reaction kinetics.

3.
Nutr Cancer ; : 1-15, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32930006

RESUMO

Differential anti-proliferative and pro-apoptotic effects of aqueous extracts of green rooibos (Rg; Aspalathus linearis) and green tea (GT; Camellia sinensis) and an aspalathin-enriched extract of green rooibos (GRE), were investigated in primary rat hepatocytes (PH) and human liver (HepG2) and colon (HT-29) cancer cells. Rooibos flavonoids, aspalathin and luteolin, and the green tea flavanol, epigallocatechin gallate (EGCG), were included to assess their contribution relative to their extract concentrations. GRE was the most effective in reducing cell growth parameters which was associated with a high total polyphenol content and high ferric reducing potential. Differential cell responses were noticed with HepG2 cells more sensitive than PH toward the induction of apoptosis by GRE. Luteolin induced apoptosis in PH and HepG2 cells while aspalathin lacked any effect. EGCG induced apoptosis in HepG2 cells while PH were resistant. HT-29 cells were resistant to apoptosis induction by the tea and pure flavonoids. Differences existed in the individual effects of the major rooibos and GT flavonoids against cell growth parameters compared to their equivalent concentrations in the extract mixtures. Diversity of the flavonoid constituents, physicochemical properties and cellular redox status governing cell survival are likely to explain the differential cell responses.

4.
Phytochem Anal ; 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32803806

RESUMO

INTRODUCTION: The minor phenolic constituents of Cyclopia pubescens Eckl. & Zeyh. are unknown and one dimensional (1D) liquid chromatography (LC) is unable to provide sufficient separation. METHODOLOGY: A two-dimensional (2D) LC method incorporating normal-phasehigh performance countercurrent chromatography (NP-HPCCC) in the first dimension (1 D) and reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) as the second dimension (2 D) was developed. The analytical HPCCC method was subsequently scaled up to semi-preparative mode and fractions pooled based on phenolic sub-groups. The phenolic compounds in selected fractions were subsequently isolated using RP-HPLC on a C18 column. Isolated compounds were identified by nuclear magnetic resonance (NMR) spectroscopy. The absolute configurations of compounds were determined by optical rotation and electronic circular dichroism spectra. Sugars were identified by gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: The comprehensive off-line 2D CCC × LC method gave a good spread of the phenolic compounds. Orthogonality calculated using both the convex hull and conditional entropy methods were 81%. High-resolution mass spectrometric fragmentation spectra obtained from a quadrupole-time-of-flight instrument and ultraviolet-visible (UV-vis) spectral data were used to (tentatively) identify 32 phenolic compounds from the analytical CCC fractions. Of the seven isolated compounds, (2S)-5-O-[α-l-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl]eriodictyol (3) and (2S)-5-O-[α-l-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl]-5,7,3',4'-tetrahydroxyflavan (4) were newly identified in all plants. The other isolated compounds were identified as (2S)-5-O-[α-l-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl]naringenin (1), R-neo-eriocitrin (2), 3-O-α-l-arabinopyranosyl-3,4-dihydroxybenzoic acid (5), 4-O-ß-d-glucopyranosyl-Z-4-hydroxycinnamic acid (6) and 4-(4'-O-ß-d-glucopyranosyl-4'-hydroxy-3'-methoxyphenyl)-2-butanone (7). CONCLUSIONS: Among the 32 compounds (tentatively) identified, only six were previously identified in Cyclopia pubescens using 1D LC. Most of the isolated compounds were also identified for the first time in Cyclopia spp., improving the knowledge of the minor phenolic compounds of this genus.

5.
Oxid Med Cell Longev ; 2020: 1948602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831989

RESUMO

Mitochondrial dysfunction plays a major role not only in the pathogenesis of many oxidative stress or age-related diseases such as neurodegenerative as well as mental disorders but also in normal aging. There is evidence that oxidative stress and mitochondrial dysfunction are the most upstream and common events in the pathomechanisms of neurodegeneration. Cyclopia species are endemic South African plants and some have a long tradition of use as herbal tea, known as honeybush tea. Extracts of the tea are gaining more scientific attention due to their phenolic composition. In the present study, we tested not only the in vitro mitochondria-enhancing properties of honeybush extracts under physiological conditions but also their ameliorative properties under oxidative stress situations. Hot water and ethanolic extracts of C. subternata, C. genistoides, and C. longifolia were investigated. Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts, at a concentration range of 0.1-1 ng/ml, had a beneficial effect on bioenergetics as it increased ATP production, respiration, and mitochondrial membrane potential (MMP) after 24 hours under physiological conditions. The aqueous extracts of C. subternata and C. genistoides, in particular, showed a protective effect by rescuing the bioenergetic and mitochondrial deficits under oxidative stress conditions (400 µM H2O2 for 3 hours). These findings indicate that honeybush extracts could constitute candidates for the prevention of oxidative stress with an impact on aging processes and age-related neurodegenerative disorders potentially leading to the development of a condition-specific nutraceutical.

6.
Food Funct ; 11(7): 6476-6486, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32627774

RESUMO

Extracts of Cyclopia species are used as food ingredients. In vitroα-glucosidase (AG) inhibition by ultrafiltered C. genistoides extract, fractions enriched in xanthones (XEF) and benzophenones (BEF), as well as mangiferin, isomangiferin, 3-ß-d-glucopyranosyliriflophenone (I3G) and 3-ß-d-glucopyranosyl-4-O-ß-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.

7.
Bioorg Chem ; 101: 103966, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32506016

RESUMO

A phytochemical survey to obtain bioactive natural products from Ajuga pantantha afforded five new neo-clerodane diterpenoids (1-5). The structures were established by analysis of their NMR spectroscopic data, and electronic circular dichroism calculations were applied to define their absolute configurations. Compounds 2 and 5 were found to have the property of inhibiting NO production (IC50 values < 40 µM). Molecular docking and Western blotting were used to study the mechanism of anti-inflammatory action. Furthermore, compound 5 with the highest activity was tested for its in vivo anti-inflammatory effects using a zebrafish model.

8.
Pharmacol Res ; 158: 104867, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32407953

RESUMO

Isoorientin is a natural C-glucosyl flavone that is generating a lot of interest due to its multiple pharmacological activities. Increasing experimental data have shown that the robust antioxidant and anti-inflammatory properties of isoorientin remain important in ameliorating a number of metabolic complications. In fact, plants rich in isoorientin have demonstrated strong ameliorative properties against complications such as hyperglycemia, hyperlipidemia, and insulin resistance. However, while such evidence is accumulating, it has not been reviewed to better inform on the therapeutic potential of this flavone in improving human health. This review examines and extrapolates available literature on the potential beneficial or detrimental effects associated with the use of isoorientin in mitigating metabolic diseases, with a specific focus on diabetes, obesity, and insulin resistance, including associated complications. The discussion includes effective doses in various experimental settings and proposed molecular mechanisms by which isoorientin may exert its therapeutic effects. In addition, the protective effects of extracts of a number of isoorientin-rich plants against metabolic complications will be highlighted.

9.
Food Funct ; 11(4): 3084-3094, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32195502

RESUMO

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.

10.
Phytomedicine ; 69: 153210, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32217447

RESUMO

BACKGROUND: More than 80% of advanced prostate cancer (PCa) cases have bone metastasis, with a 5-year survival rate of 25%. Previously, we reported that GRT, a standardized, pharmaceutical-grade aspalathin-rich extract (12.78 g aspalathin/100 g extract), prepared from green rooibos produced from the leaves and fine stems of Aspalathus linearis, inhibits the proliferation of PCa cells, meriting this investigation to determine if GRT can suppress the migration and invasion of castration-resistant prostate cancer (CRPC) cells. PURPOSE: In the present study, we investigated whether GRT extract can interfere with the migration and invasion of human CRPC cells. METHODS: Transwell assays were used to explore the effects of GRT on the migration and invasion of CRPC cells. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism(s). RESULTS: Treatment with 25-100 µg/ml GRT suppressed the migration and invasion of LNCaP C4-2B and 22Rv1 CRPC cells. MWA and Western blot analysis indicated that GRT treatment suppressed the protein level of yes-associated protein (YAP), macrophage stimulating 1 protein (MST1), phospho-MST1/phospho-MST2 T183/T180, and paxillin, but increased the abundance of E-cadherin. Over-expression of YAP rescued the suppressive effects of GRT on migration and invasion of CRPC cells. Treatment with the major flavonoid of GRT - the C-glucosyl dihydrochalcone, aspalathin - at a concentration of 75-100 µg/ml also reduced the migration and invasion of CRPC cells, and the inhibition was partially rescued by YAP over-expression. CONCLUSIONS: GRT treatment suppresses the migration and invasion of CRPC cells via inhibition of YAP signaling and paxillin.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Aspalathus/química , Chalconas/farmacologia , Extratos Vegetais/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Masculino , Paxilina/metabolismo , Extratos Vegetais/química , Neoplasias de Próstata Resistentes à Castração/patologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo
11.
Front Pharmacol ; 10: 1243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708777

RESUMO

An aspalathin-rich green rooibos extract (Afriplex GRT™) has demonstrated anti-diabetic and hypolipidemic properties, while also moderately inhibiting CYP3A4 activity, suggesting a potential for herb-drug interaction. The present study, therefore, evaluated the effects of orally administered GRT on the pharmacokinetics of atorvastatin and metformin in Wistar rats. Wistar rats were orally treated with GRT (50 mg/kg BW), atorvastatin (40 mg/kg BW) or metformin (150 mg/kg BW) alone or 50 mg/kg BW GRT in combination with 40 mg/kg BW atorvastatin or 150 mg/kg BW metformin. Blood samples were collected at 0, 10, and 30 min and 1, 2, 4, 6, and 8 h and plasma samples obtained for Liquid chromatography-mass spectrometry (LC-MS/MS) analyses. Non-compartment and two-compartment pharmacokinetic parameters of atorvastatin and metformin in the presence or absence of GRT were determined by PKSolver version 2.0 software. Membrane transporter proteins, ATP-binding cassette sub-family C member 2 (Abcc2), solute carrier organic anion transporter family, member 1b2 (Slco1b2), ATP-binding cassette, sub-family B (MDR/TAP), member 1A (Abcb1a), and organic cation transporter 1 (Oct1) mRNA expression were determined using real-time PCR expression data normalized to ß-actin and hypoxanthine-guanine phosphoribosyltransferase (HPRT), respectively. Co-administration of GRT with atorvastatin substantially increased the maximum plasma concentration (Cmax) and area of the plasma concentration-time curve (AUC0-8) of atorvastatin by 5.8-fold (p = 0.03) and 5.9-fold (p = 0.02), respectively. GRT had no effect on the plasma levels of metformin. GRT increased Abcc2 expression and metformin downregulated Abcb1a expression while the combination of GRT with atorvastatin or metformin did not significantly alter the expression of Slco1b1 or Oct1 did not significantly alter the expression of Sclo1b2 or Oct1. Co-administration of GRT with atorvastatin in rats may lead to higher plasma concentrations and, therefore, to an increase of the exposure to atorvastatin.

12.
Biomed Pharmacother ; 120: 109439, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31590126

RESUMO

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.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Cyclopia (Planta)/química , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Fármacos Antiobesidade/farmacocinética , Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais , Humanos , Fenóis , Xantonas
13.
Antioxidants (Basel) ; 8(10)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640245

RESUMO

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.

14.
Food Res Int ; 125: 108519, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31554050

RESUMO

Variation in the bitter taste of Cyclopia genistoides (honeybush) herbal tea and reported modulation between its major xanthones, mangiferin and isomangiferin, prompted further investigation into the potential modulatory effects of honeybush phenolics. Combinations of crude benzophenone (BF)-, xanthone (XF)-, and flavanone (FF)-rich fractions and their major individual phenolic compounds were analysed by descriptive sensory analysis. The fractions were prepared from a bitter, hot water extract of green C. genistoides. Fraction BF, which is below the bitter threshold (intensity 10 on 100-point scale), enhanced the bitter intensity of XF and FF slightly (p < 0.05), although none of the major individual benzophenones retained this bitter enhancing effect. On the contrary, 3-ß-d-glucopyranosyl-4-ß-d-glucopyranosyloxyiriflophenone, the major benzophenone in BF, significantly (p < 0.05) decreased the bitter taste of XF, at a low concentration, whereas FF suppressed the bitter intensity of XF and mangiferin, the major xanthone present in XF. Hesperidin, however, had no effect on the bitter intensity of XF. In contrast, (2S)-5-[α-L-rhamnopyranosyl-(1→2)-ß-d-glucopyranosyloxy]-naringenin, the major compound of FF, significantly (p < 0.05) enhanced the bitter taste of XF when added at concentrations comparable to that of 'fermented' honeybush tea infusions. The concentration-dependence of these bitter taste interactions may be responsible for the variable bitter intensity of C. genistoides herbal tea.


Assuntos
Benzofenonas/análise , Fabaceae/química , Flavanonas/análise , Chás de Ervas/análise , Cromatografia Líquida de Alta Pressão , Humanos , Paladar/fisiologia
15.
Phytomedicine ; 64: 153068, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31419729

RESUMO

BACKGROUND: Androgen ablation therapy is the primary treatment for metastatic prostate cancer (PCa). However, the majority of PCa patients receiving the androgen deprivation therapy develop recurrent castration-resistant prostate cancer (CRPC) within two years. Chemotherapies show little effect on prolonging survival of CRPC patients and new treatments are needed. Previous studies reported that the extracts from rooibos (Aspalathus linearis) exhibit chemopreventive properties in some cancer models, including skin, liver and oesophagus cancers in animals. We therefore investigate if extracts from rooibos can suppress the proliferation of CRPC cells. PURPOSE: We investigated whether an aspalathin-rich green rooibos extract (GRT™; 12.78 g aspalathin/100 g extract) demonstrates anti-cancer activity against CRPC cells. METHODS: High performance liquid chromatography (HPLC) was used to profile the major flavonoids in GRT. Hoechst-dye proliferation assay, 3,4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) viability assay and flow cytometry assay were used to explore the effects of GRT on the proliferation and cell cycle progression of CRPC cells. Comet assay was used to survey whether GRT induces apoptosis in CRPC cells. LNCaP 104-R1 xenograft nude mice model was used to determine the inhibitory effect of GRT on CRPC tumors in vivo. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism. RESULTS: GRT contained aspalathin as the most abundant flavonoid. GRT suppressed the proliferation and survival of LNCaP 104-R1, LNCaP FGC and PC-3 PCa cells. Flow cytometry analysis showed that GRT decreased the population of PCa cells in S phase but increased the cell population in G2/M phase. Comet assay confirmed that GRT induced apoptosis in LNCaP 104-R1 cells. Gavage of 400 mg/kg GRT suppressed LNCaP 104-R1 xenografts in castrated nude mice. MWA and Western blot analysis indicated that GRT treatment suppressed Akt1, phospho-Akt Ser473, Cdc2, Bcl-2, TRAF4 and Aven, but increased activated Caspase 3, cytochrome c, and p27Kip1. Overexpression of Akt rescued the suppressive effects of GRT on CRPC cells. Co-treatment of GRT with Bcl-2 inhibitor ABT-737, PI3K inhibitor LY294002 and Akt inhibitor GSK 690693 exhibited additive inhibitory effect on proliferation of CRPC cells. CONCLUSIONS: GRT suppresses the proliferation of CRPC cells via inhibition of Akt signaling.


Assuntos
Antineoplásicos/farmacologia , Aspalathus/química , Chalconas/farmacologia , Extratos Vegetais/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores
16.
Food Chem ; 292: 121-128, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054655

RESUMO

Ultrafiltration of Cyclopia genistoides extract was optimised to increase its benzophenone and xanthone content as quantified using HPLC-DAD. Regenerated cellulose (RC) and polyethersulphone membranes with molecular weight cut-offs of 10 and 30 kDa were evaluated in terms of compound enrichment, permeate flux and permeate yield, using dead-end ultrafiltration. Compound enrichment was subsequently optimised using the 10 kDa RC membrane and tangential flow ultrafiltration (TFU). The effect of extract composition on compound enrichment, due to natural variation in the source material, was assessed using extracts from different batches of plant material (n = 11). Transmembrane pressure and feed flow rate affected (p < 0.05) process efficiency (mean permeate flux, compound enrichment and membrane fouling). TFU achieved ≥20% enrichment of the target compounds, proving its suitability for preparation of a nutraceutical extract of C. genistoides.


Assuntos
Benzofenonas/análise , Fabaceae/metabolismo , Extratos Vegetais/química , Ultrafiltração/métodos , Xantonas/análise , Benzofenonas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Membranas Artificiais , Xantonas/isolamento & purificação
17.
PLoS One ; 14(5): e0216172, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31048842

RESUMO

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.


Assuntos
Chalconas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Glicemia/metabolismo , Linhagem Celular , Chalconas/metabolismo , Glucose/metabolismo , Hepatócitos/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Resistência à Insulina/fisiologia , Fígado/metabolismo , Mitocôndrias/metabolismo , Modelos Biológicos , Palmitatos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Food Res Int ; 121: 185-196, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31108739

RESUMO

Phenolic compounds of Aspalathus linearis (rooibos) are susceptible to oxidation during "fermentation", a process characterized by the formation of a red-brown leaf color. The role of enzymes in this process is not yet understood. An experiment with dried green rooibos plant material pre-treated at 170 °C for 30 min to denature and "inactivate" endogenous enzymes was conducted to confirm the role of oxidative enzymes. The phenolic composition of "enzyme inactivated" plant material was not significantly (p ≥ .05) affected by simulated fermentation, compared to control samples, as determined using piece-wise multivariate analysis of variance for successive time intervals. This proves that rooibos enzymes participate in the oxidation of phenolic compounds during fermentation of the plant material. A kinetic modeling approach was subsequently used to establish reaction kinetic parameters for selected rooibos phenolic compounds. The degradation of aspalathin and nothofagin and formation of eriodictyol glucosides during simulated fermentation at four temperatures from 37 to 50 °C were best described by the fractional conversion model based on first-order kinetics (r2 > 0.98), which allows for non-zero equilibrium concentrations. The extent of degradation for other compounds was too low to enable kinetic modeling. Reaction rates for the degradation/formation of phenolic compounds during fermentation followed the Arrhenius law. Less phenolic degradation (higher equilibrium concentration), but a higher reaction rate constant, was observed at higher temperatures, which could possibly be attributed to inactivation of enzymes.


Assuntos
Aspalathus/enzimologia , Aspalathus/metabolismo , Fermentação/fisiologia , Fenóis/metabolismo , Cinética , Modelos Biológicos , Oxirredução , Temperatura
19.
Molecules ; 24(9)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052590

RESUMO

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.


Assuntos
Chalconas/farmacologia , LDL-Colesterol/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica/efeitos adversos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores , Glicemia/efeitos dos fármacos , Chlorocebus aethiops , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Lipídeos/sangue , Lipoproteínas LDL/sangue , Masculino , Extratos Vegetais/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/sangue
20.
Anal Chim Acta ; 1059: 16-27, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30876628

RESUMO

Instrumental signals of samples cannot be compared and/or analysed directly if their concentrations are unknown. Differences in overall concentration need to be removed at the data normalization step. The choice of normalization method has a profound effect on the final results of data analysis, and especially on biomarker identification. One of the possible approaches to deal with the 'size effect' is to work with size-irrelevant (log) ratios instead of the original variables. In the presented study, the performance of log-ratio methods, namely pairwise log-ratio (plr) and centered log-ratio (clr), is discussed for real and simulated data sets with different characteristics. It was found that the clr method can lead to distribution of local differences along an entire signal and as such, it should be avoided in all studies aiming to identify biomarkers.


Assuntos
Biomarcadores/análise , Análise de Dados , Aspalathus/química , Cromatografia Líquida de Alta Pressão/estatística & dados numéricos , Análise dos Mínimos Quadrados
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