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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]

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

Phytochemical investigation of aerial parts of Helichrysum niveum (H. niveum) using different chromatographic methods including semi-preparative HPLC afforded three new (1-3) and six known (4-10) acylphloroglucinols alongside a known dialcohol triterpene (11). The structures of the isolated compounds were characterized accordingly as 1-benzoyl-3 (3-methylbut-2-enylacetate)-phloroglucinol (helinivene A, 1), 1-benzoyl-3 (2S-hydroxyl-3- methylbut-3-enyl)-phloroglucinol (helinivene B, 2), 8-(2-methylpropanone)-3S,5,7-trihydroxyl- 2,2-dimethoxychromane (helinivene C, 3), 1-(2-methylbutanone)-4-O-prenyl-phloroglucinol (4), 1-(2-methylpropanone)-4-O-prennyl-phloroglucinol (5), 1-(butanone)-3-prenyl-phloroglucinol (6), 1-(2-methylbutanone)-3-prenyl-phloroglucinol (7), 1-butanone-3-(3-methylbut-2-enylacetate)- phloroglucinol (8), 1-(2-methylpropanone)-3-prenylphloroglucinol (9), caespitate (10), and 3â-24-dihydroxyterexer-14-ene (11). Excellent total antioxidant capacities were demonstrated by helinivenes A and B (1 and 2) when measured as oxygen radicals absorbance capacity (ORAC), ferric-ion reducing antioxidant power (FRAP), trolox equivalent absorbance capacity (TEAC) and including the inhibition of Fe2+-induced lipid peroxidation (IC50 = 5.12 ± 0.90; 3.55 ± 1.92) ìg/mL, while anti-tyrosinase activity at IC50 = 35.63 ± 4.67 and 26.72 ± 5.05 ìg/mL were also observed for 1 and 2, respectively. This is the first chemical and in vitro biological study on H. niveum. These findings underpin new perspectives for the exploitation of these natural phenolic compounds in applications such as in the natural cosmeceutical and pharmaceutical sectors. [ABSTRACT FROM AUTHOR]

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

The possible protective effects of an aqueous rooibos extract (Aspalathus linearis), red palm oil (RPO) (Elaeis guineensis), or their combination on tert-butyl-hydroperoxide-(t-BHP-)induced oxidative hepatotoxicity in Wistar rats were investigated. tert-butyl hydroperoxide caused a significant (P < 0.05) elevation in conjugated dienes (CD) and malondialdehyde (MDA) levels, significantly (P < 0.05) decreased reduced glutathione (GSH) and GSH : GSSG ratio, and induced varying changes in activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase in the blood and liver. This apparent oxidative injury was associated with histopathological changes in liver architecture and elevated levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). Supplementation with rooibos, RPO, or their combination significantly (P < 0.05) decreased CD and MDA levels in the liver and reduced serum level of ALT, AST, and LDH. Likewise, changes observed in the activities of antioxidant enzymes and impairment in redox status in the erythrocytes and liver were reversed. The observed protective effects when rooibos and RPO were supplemented concomitantly were neither additive nor synergistic. Our results suggested that rooibos and RPO, either supplemented alone or combined, are capable of alleviating t-BHP-induced oxidative hepatotoxicity, and the mechanism of this protection may involve inhibition of lipid peroxidation and modulation of antioxidants enzymes and glutathione status. [ABSTRACT FROM AUTHOR]

Rooibos is brewed from the medicinal plant Aspalathus linearis. It has a well-established wide spectrum of bio-activity properties, which in part may be attributed to the phenolic antioxidant power. The antioxidant capacity (AOC) of rooibos is related to its total phenolic content (TPC). The relation between TPC and AOC of randomly selected 51 fermented (FR) and 47 unfermented (UFR) rooibos samples was studied after extraction using water and methanol separately. The resulted extracts were assessed using two antioxidant assays, trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). The results were analyzed using both simple statistical methods and machine learning. The analysis showed different trends of TPC and AOC correlations of FR and UFR samples, depending on the solvent used for extraction. The results of the water extracts showed similar TPC and higher AOC of FR than UFR samples, while the methanolic extracted samples showed higher TPC and AOC of UFR than FR. As a result, the methanolic extracts showed better agreement between TPC and AOC than water extracts. Possible explanations are given for these observed results. Although, the current literature demonstrates direct correlations of the TPC and AOC of rooibos water extracts. This study showed deviation and highlighted the importance of solvent selection and analysis methodology as an important factor in determining the TPC/AOC correlation and subsequently the expectation of the actual health benefits of rooibos herbal tea. In particular, unfermented and fermented samples can be accurately identified on the basis of a combination of assays (any two of TPC, FRAP and TEAC), especially if methanol is the solvent used. Machine learning analysis of assay data provides nearly identical results with classical statistical analytical methods. This is the first report on machine learning analysis and comparison of the TPC and AOC of rooibos herbal tea extracted with methanol and water, and highlights the importance of using methanol as a solvent to evaluate its AOC. [ABSTRACT FROM AUTHOR]

Abstract: The chemoprotective properties of unfermented and fermented rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) herbal teas, and green and black teas (Camellia sinensis) were investigated against fumonisin B1 (FB1) promotion in rat liver utilizing diethylnitrosamine (DEN) as cancer initiator. The various teas differently affected the clinical chemical parameters associated with liver and kidney damage associated with FB1 suggesting specific FB1/iron/polyphenolic interactions. Green tea enhanced (P <0.05) the FB1-induced reduction of the oxygen radical absorbance capacity, while fermented herbal teas and unfermented honeybush significantly (P <0.05) decreased FB1-induced lipid peroxidation in the liver. The teas exhibited varying effects on FB1-induced changes in the activities of catalase, glutathione peroxidase (GPx) glutathione reductase (GR) as well as the glutathione (GSH) status. Unfermented rooibos and honeybush significantly (P <0.05) to marginally (P <0.1) reduced the total number of foci (>10μm), respectively, while all the teas reduced the relative amount of the larger foci. Fermentation seems to reduce the protective effect of the herbal teas. Differences in the major polyphenolic components and certain FB1/polyphenolic/tissue interactions may explain the varying effects of the different teas on the oxidative parameters, hepatotoxic effects and cancer promotion in rat liver. [Copyright &y& Elsevier]

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

Forest pockets adjacent to cities are impacted by atmospheric pollution containing metals arising from urban activities. Elevated concentrations of metals have been found in forest soils and contamination thereof threatens soil biodiversity. Metals are known to induce oxidative stress and metal cytotoxicity in organisms has been linked to oxidative damage, which may threaten the health of forest soil and its biodiversity. Pill millipedes in the Afromontane forest pockets in Cape Town, South Africa are exposed to a combination of metals, arising from various sources of pollution. The objectives of this investigation were to determine the level of metal bioaccumulation and oxidative stress in millipedes experimentally exposed to a cocktail of metals. The millipedes were exposed to a high and low concentration aluminium, iron and manganese cocktail for 6 weeks. The experimental exposure resulted in bioaccumulation of these metals in millipedes in their different exposure groups. The higher tGSH concentrations, indicated activation of the endogenous antioxidant system, and the higher MDA levels, suggests lipid peroxidation by means of the increased generation of free radicals, which suggests that the pill millipedes have experienced induced oxidative stress. [ABSTRACT FROM AUTHOR]

The re-investigation of a methanolic extract of Salvia africana-lutea collected from the Cape Floristic Region, South Africa (SA), afforded four new abietane diterpenes, namely 19-acetoxy-12-methoxycarnosic acid (1), 3β-acetoxy-7α-methoxyrosmanol (2), 19-acetoxy-7α-methoxyrosmanol (3), 19-acetoxy-12-methoxy carnosol (4), and two known named clinopodiolides A (5), and B (6), in addition to four known triterpenes, oleanolic, and ursolic acids (7, 8), 11,12-dehydroursolic acid lactone (9) and β-amyrin (10). The chemical structural elucidation of the isolated compounds was determined on the basis of one and two dimensional nuclear magnetic resonance (1D and 2D NMR), high-resolution mass spectrometry (HRMS), ultra violet (UV), fourier transform infrared (IR), in comparison with literature data. The in vitro bio-evaluation against alpha-glucosidase showed strong inhibitory activities of 8, 10, and 7, with the half inhibitory concentration (IC50) values of 11.3 ± 1.0, 17.1 ± 1.0 and 22.9 ± 2.0 µg/mL, respectively, while 7 demonstrated the strongest in vitro alpha-amylase inhibitory activity among the tested compounds with IC50 of 12.5 ± 0.7 µg/mL. Additionally, some of the compounds showed significant antioxidant capacities. In conclusion, the methanolic extract of S. africana-lutea is a rich source of terpenoids, especially abietane diterpenes, with strong antioxidant and anti-diabetic activities that can be helpful to modulate the redox status of the body and could therefore be an excellent candidate for the prevention of the development of diabetes, a disease where oxidase stress plays an important role. [ABSTRACT FROM AUTHOR]

The antioxidant content, capacity and certain oxidative stress parameters were investigated in salinity stressed Lactuca sativa L. 'Eish!' with the addition of exogenous silicon (Si). No significant changes were shown for total polyphenol concentrations in any of the experimental plants. Applications of 4 mM Si significantly increased oxygen radical absorbance capacity analysis (ORAC) values at both 30 and 60 mM NaCl. The redox status of glutathione was also improved with a significant increase in reduced glutathione (GSH) in 2 mM Si treated plants at 30 mM NaCl. Increases in both GSH and oxidised glutathione (GSSG) were noted at 60 mM NaCl. The activity of catalase (CAT) was significantly decreased with the addition of 1 and 4 mM Si at 30 mM NaCl. Lipid peroxidation (measured as thiobarbituric acid reactive substances, TBARS) was not influenced by the different Si concentrations. These results suggest that applications of Si could be beneficial with regards to the modulation of oxidative stress in salinity stressed lettuce and should be considered as an addition when cultivating lettuce. [ABSTRACT FROM AUTHOR]

Glioblastoma, the most aggressive brain cancer, is challenging to treat owing to the difficulty of crossing the blood-brain barrier, high recurrence rates and significant mortality. This review highlights the potential of green synthesis methods in developing metal nanoparticles (MNPs) as a sustainable solution for drug delivery systems targeting glioblastoma. We explore the unique properties and modes of action of MNPs synthesised through eco-friendly processes by focusing on their bioavailability and precision in brain targeting, and discuss the potential of MNPs to target glioblastoma at the molecular level. Integrating green synthesis into cancer therapeutics represents a novel paradigm shift towards treatments with higher efficacy and lower environmental impact, offering hope in the fight against glioblastoma., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fumonisin B 1 (FB 1 ) is etiologically linked to cancer, yet the underlying mechanisms remain largely unclear. It is also not known if mitochondrial dysfunction is involved as a contributor to FB 1 -induced metabolic toxicity. This study investigated the effects of FB 1 on mitochondrial toxicity and its implications in cultured human liver (HepG2) cells. HepG2 cells poised to undergo oxidative and glycolytic metabolism were exposed to FB 1 for 6 h. We determined mitochondrial toxicity, reducing equivalent levels and mitochondrial sirtuin activity using luminometric, fluorometric and spectrophotometric methods. Molecular pathways involved were determined using western blots and PCR. Our data confirm that FB 1 is a mitochondrial toxin capable of disrupting the stability of complexes I and V of the mitochondrial electron transport and decreasing the NAD:NADH ratio in galactose supplemented HepG2 cells. We further showed that in cells treated with FB 1 , p53 acts as a metabolic stress-responsive transcription factor that induces the expression of lincRNA-p21, which plays a crucial role in stabilising HIF-1α. The findings provide novel insights into the impact of this mycotoxin in the dysregulation of energy metabolism and may contribute to the growing body of evidence of its tumor promoting effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fumonisins are a family of potentially carcinogenic mycotoxins produced by Fusarium verticillioides. Several fumonisins have been identified with fumonisin B 1 (FB 1 ) being the most toxic. The canonical mechanism of FB 1 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 FB 1 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 FB 1 . 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 FB 1 toxicoses. In the search for a means to address FB 1 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 FB 1 -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 FB 1 ., (© 2020 John Wiley & Sons, Ltd.)

Background: Rooibos types and forms and how prepared and flavoured influence the total polyphenol content and total antioxidant capacity (TAC)., Aim: To denote an optimal rooibos cup as having the highest total polyphenol content and TAC, considering the different types, forms, preparation methods and flavourings and amounts (Phase 1), and determine the demographic, lifestyle and rooibos consumption characteristics of adult rooibos consumers, and the association of these characteristics with drinking the optimal cup (Phase 2)., Setting: Assays: Oxidative Stress Research Centre, Cape Peninsula University of Technology; Consumer survey: George area, South Africa., Method: Phase 1 entailed determining the total polyphenol content (Folin-Ciocalteau method) and TAC (Trolox equivalent antioxidant capacity and ferric-reducing antioxidant power assay) of the prepared rooibos samples. For Phase 2, a developed, pilot tested questionnaire was used to profile adult rooibos consumers., Results: Phase 1: the following samples delivered higher total polyphenol content and TAC: green (type), green leaves and powdered extract (forms), and sample steeped for 10 min or longer (preparation method). The identified optimal cup was sample steeped for 10 min or longer. Phase 2: a total of 308 respondents completed the questionnaire. Few consumed more than one rooibos cup per day (25.3%; n = 78) and the optimal cup (15.9%; n = 49). These latter respondents comprised those who steeped rooibos in a teapot (not a cup or mug) ( p < 0.05)., Conclusions: The optimal cup was identified as sample steeped for 10 min or longer. The rooibos consumers did not consume it sufficiently, nor steeped it long enough., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this manuscript., (© 2019. The Authors.)