Phenolic composition and bioactive properties of cell wall preparations and whole grains of selected cereals and legumes

Phenolic compounds are associated with cell walls in cereals and legumes. Phenolic composition and bioactive properties of cell walls and whole grain of sorghum, teff and cowpea were determined.Whole grain extracts had higher total phenolic content (630–2,782 mg CE/g) and total flavonoid content (0.033– 0.17 mg CE/g) than cell wall extracts (261–1,005 and 0.011–0.047 mg CE/g, respectively). Similar trends were observed for 2,2’-azinobis (3-ethylbenzothiazoline- 6 sulfonic acid) radical scavenging (whole grain: 30–87; cell wall: 22 mM TE/g), oxygen radical absorbance capacity (whole grain: 47–964; cell wall: 40–183 mM TE/g) and ferric reducing power (whole grain: 85–279; cell wall: 41–95 mg vitamin C equivalent/g). Whole grains contained both phenolic acids and flavonoids. Ferulic acid was a major component of cell walls.Whole grain and cell wall extracts inhibited low-density lipoprotein oxidation and protected against oxidative DNA damage. Cereal and legume cell walls may be considered important potential contributors to human health because of their phenolic composition.South African National Research Foundation including the award of a post-doctoral fellowship for S.O. Salawu.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1745-45142015-02-28hb201

Exploring the anti-proliferative activity of Pelargonium sidoides DC with in silico target identification and network pharmacology

Pelargonium sidoides DC (Geraniaceae) is a medicinal plant indigenous to Southern Africa that has been widely evaluated for its use in the treatment of upper respiratory tract infections. In recent studies, the anti-proliferative potential of P. sidoides was shown, and several phenolic compounds were identified as the bioactive compounds. Little, however, is known regarding their anti-proliferative protein targets. In this study, the anti-proliferative mechanisms of P. sidoides through in silico target identification and network pharmacology methodologies were evaluated. The protein targets of the 12 phenolic compounds were identified using the target identification server PharmMapper and the server for predicting Drug Repositioning and Adverse Reactions via the Chemical–Protein Interactome (DRAR-CPI). Protein–protein and protein–pathway interaction networks were subsequently constructed with Cytoscape 3.4.0 to evaluate potential mechanisms of action. A total of 142 potential human target proteins were identified with the in silico target identification servers, and 90 of these were found to be related to cancer. The protein interaction network was constructed from 86 proteins involved in 209 interactions with each other, and two protein clusters were observed. A pathway enrichment analysis identified over 80 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched with the protein targets and included several pathways specifically related to cancer as well as various signaling pathways that have been found to be dysregulated in cancer. These results indicate that the anti-proliferative activity of P. sidoides may be multifactorial and arises from the collective regulation of several interconnected cell signaling pathways.https://link.springer.com/journal/110302018-11-18hj2017AnatomyBiochemistr

Ultrastructural, confocal and viscoelastic characteristics of whole blood and plasma after exposure to cadmium and chromium alone and in combination : an ex vivo study

BACKGROUND/AIMS : Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the first to be affected following exposure and adverse effects on blood coagulation can lead to associated thrombotic disease. Although the plasma levels and the effects of cadmium (Cd) and chromium (Cr) on erythrocytes and lymphocytes have been described, the environmental exposure to heavy metals are not limited to a single metal and often involves metal mixtures, with each metal having different rates of absorption, different cellular, tissue, and organ targets. Therefore the aim of this study is to investigate the effects of the heavy metals Cd and Cr alone and whether Cr synergistically increases the effect of Cd on physiological important processes such as blood coagulation. METHODS : Human blood was exposed to the heavy metals ex vivo, and thereafter morphological analysis was performed with scanning electron- and confocal laser scanning microscopy (CLSM) in conjunction with thromboelastography®. RESULTS : The erythrocytes, platelets and fibrin networks presented with ultrastructural changes, including varied erythrocytes morphologies, activated platelets and significantly thicker fibrin fibres in the metal-exposed groups. CLSM analysis revealed the presence of phosphatidylserine on the outer surface of the membranes of the spherocytic erythrocytes exposed to Cd and Cr alone and in combination. The viscoelastic analysis revealed only a trend that indicates that clots that will form after heavy metal exposure, will likely be fragile and unstable especially for Cd and Cr in combination. CONCLUSION : This study identified the blood as an important target system of Cd and Cr toxicity.The National Research Foundation (NRF) (Grant number: 92768).am2017AnatomyPhysiolog

Induction of hepatic portal fibrosis, mitochondria damage, and extracellular vesicle formation in Sprague-Dawley rats exposed to copper, manganese, and mercury, alone and in combination

Increased anthropogenic activity and subsequent environmental exposure to heavy metals induce the production of reactive oxygen species (ROS), which increases oxidative stress and the risk of associated diseases. The aim of this study, in a subacute model of toxicity, was to investigate the effects of copper (Cu), manganese (Mn), and mercury (Hg) alone and in combination on the liver tissue of male Sprague-Dawley rats, exposed orally to 100 times the World Health Organization’s acceptable water limits of each metal. General histological alterations as well as ultrastructural changes were investigated using light microscopy and transmission electron microscopy (TEM) respectively. Exposure to Cu, Mn, and Hg, alone and in combinations, caused hydropic swelling of the hepatocytes, dilation of the sinusoids, formation of binucleated hepatocytes with an increased inflammatory cell accumulation at the portal triad. Increased collagen deposition with associated fibrosis was also observed. Evaluation of hepatocyte ultrastructure revealed mitochondrial membrane damage and inner membrane swelling especially for hepatocytes exposed to Mn. Extracellular vesicle (EV) formation was observed in the liver tissue of all exposed rats. Furthermore, increased damage observed for metal combinations was possibly due to synergism. In conclusion, Cu, Mn, and Hg alone and as part of a mixture cause cellular damage, inflammation, and fibrosis increasing the risk of associated diseases.The National Research Foundation (NRF)http://www.tandfonline.com/loi/iusp202021-02-24hj2020Anatom

Activity-guided isolation and identification of the major antioxidant and anticancer compounds from a commercial Pelargonium sidoides tincture

Extracts prepared from the roots of Pelargonium sidoides (DC) are commercially available for the treatment of respiratory related conditions. Recently, a commercial radix mother tincture of this plant was shown to have both antioxidant and anticancer effects especially related to the G0/G1 block in the Jurkat E6.1 cell line (unpublished results). Fractions were prepared by semi-preparative HPLC, and their antioxidant and anticancer activities were determined. The more hydrophilic fractions isolated namely F6-F12 were all found to have strong reducing capacities and were able to scavenge peroxyl radicals. In the human lung cell line, NCI-H460, significant cellular antioxidant effects were observed. Anticancer activity was evaluated in the NCI-pre-screen panel (NCI-H460, MCF-7 and SF-268) and the Jurkat E6.1 cell line. Fractions F7, F9 and F12 were found to inhibit the cell growth of these four cell-lines (p < 0.05), especially the Jurkat E6.1 cell line with the sulforhodamine B assay. Mass spectrometry analysis revealed that these active fractions contained several polyphenolic compounds such as gallic acid, trihydroxycoumarin, dihydroxycoumarin sulfates, proanthocyanidins and phenolic glycosides. A phenolic acid glycoside sulfate not previously shown in Pelargonium sidoides extracts was also isolated. In conclusion, the antioxidant and/or anticancer activity of the Pelargonium sidoides tincture may be attributed to the presence of these polyphenolics.National Research Foundation of South Africahttp://link.springer.com/journal/442016-11-30hb201

Sibutramine, a serotonin-norepinephrine reuptake inhibitor, causes fibrosis in rats

Sibutramine hydrochloride monohydrate is a weight loss agent indicated for the treatment of obesity. Although it has been banned from most markets, studies are still relevant as it is often a hidden ingredient in herbal and over the counter slimming products. Sibutramine induces liver fibrosis with steatosis in female Sprague-Dawley rats fed a high-energy diet without significant weight gain. In this study, using the same animal model, the effect of Sibutramine on lung morphology was investigated using histological evaluation of the terminal bronchiole and transmission electron microscopy evaluation of the respiratory tissue. From these results Sibutramine was found to induce lung fibrosis in Sprague-Dawley rats as increased collagen synthesis, mast cell accumulation and aggregates of Bronchus Associated Lymphoid Tissue (BALT) in the terminal bronchiole as well as increased collagen deposition in the respiratory tissue was seen.National Research Foundation (NRF)http://www.elsevier.com/locate/etap2016-07-31hb201

Rats on a high-energy diet showing no weight gain present with ultrastructural changes associated with liver fibrosis

Sibutramine is widely used as a weight-loss substance in the treatment of obesity and is a selective inhibitor of the neuronal reuptake of serotonin and noradrenaline. Although banned, it is often a hidden ingredient in herbal and dietary supplements that are widely used by the general public. Various weight loss products, including sibutramine, have successfully been tested in animal models of diet-induced obesity. In the female Sprague-Dawley rat model, fed a high-energy diet that did not produce a significant increase in BMI, the cellular structure of the liver was evaluated using transmission electron microscopy. Compared to controls showing no damage, the livers of rats fed a high-energy diet were found to have increased fibrosis without steatosis, while for rats fed high-energy diet with sibutramine, fibrosis was increased and steatosis had developed. In conclusion, in female rats fed a high-energy diet that does not result in weight gain hepatic fibrosis occurs without steatosis. In these rats the co-administration of sibutramine increases the degree of fibrosis and steatosis develops. Although it has been widely believed that sibutramine is not hepatotoxic, this study clearly shows that at an ultrastructural level, rats fed a high-energy diet treated with sibutramine show signs of hepatotoxicity.http://www.tandfonline.com/loi/iusp20hb2016Anatom

Effects of mandrax and cannabis on the cellular function of chick embryonic neurons

Cannabis and Mandrax abuse is unique to South Africa; and most research has focused on the socio-economic impact rather than the adverse effects on the developing brain. Therefore, the aim of this study is to determine the effects of Mandrax and Cannabis alone and in combination on the developing brain by using primary and suspension cultures of the chick embryo brain. Exposure of primary chick embryo neuronal (CEN) cultures to the carrier ethanol, Mandrax and Cannabis, for 24 h resulted in a significant dose dependent decrease in cell number for Mandrax alone. Increasing concentrations of Cannabis in combination with Mandrax inhibited the toxic effect of Mandrax. In CEN suspensions, Mandrax alone induced a significant time–concentration dependent decrease in esterase activity following 1 and 4 h exposure. In combination with Cannabis, a significant increase in esterase activity was observed after 4 h exposure. In conclusion Mandrax is toxic to CEN cells in vitro while Cannabis seemed to have a protective effect; however, this study does not investigate the abuse of these drugs in the form commonly abused, namely inhaled smoke

Adverse cardiovascular effects of exposure to cadmium and mercury alone and in combination on the cardiac tissue and aorta of Sprague–Dawley rats

The aim of this study was to identify cardiovascular effects of relevant concentrations of Cd and Hg alone and in combination as a mixture in water. This was achieved by administering to male Sprague–Dawley rats via gavage 0.62 mg/kg Cd or 1.23 mg/kg Hg, or a combination of 0.62 mg/kg Cd and 1.23 mg/kg Hg in the co-exposure group for 28 days. Concentrations were the rat equivalence dosages of 1,000 times the World Health Organization’s limits of 0.003 mg/L and 0.006 mg/L for Cd and Hg, respectively, for water. With termination, blood levels of the metals were increased. For all metal exposed groups, histological evaluation and transmission electron microscopy of the myocardium revealed myofibrillar necrosis, increased fibrosis, vacuole formation and mitochondrial damage. Cd caused the most mitochondrial damage while Hg to a greater degree induced fibrosis. In the aorta, both Cd and Hg also increased collagen deposition adversely altering the morphology of the fenestrated elastic fibers in the tunica media. Co-exposure resulted in increased cardiotoxicity with increased mitochondrial damage, fibrosis and distortion of the aortic wall as a result of increased collagen deposition, as well as altered elastin deposition, fragmentation and interlink formation. These are typical features of oxidative damage that correlates with a phenotype of premature ageing of the CVS that potentially can lead to hypertension and premature cardiac failure.The National Research Foundationhttp://www.tandfonline.com/loi/lesa202022-03-15hj2022Anatom

Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G(0)/G(1) arrest and apoptosis in Jurkat leukaemia cells

CONTEXT : Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown root extracts rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. OBJECTIVE : This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). MATERIALS AND METHODS : The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukemia cell line at concentrations of 0-150 μg/mL. Effect on cell growth was determined with sulforhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. Effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. RESULTS : Dihydroxycoumarin sulfates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 of 9.7 μg/mL). The PST arrested Jurkat cells at G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. CONCLUSION : We present evidence that Pelargonium sidoides has cancer cell type specific antiproliferative effects and may be a source of novel anticancer molecules.National Research Foundation of South Africa.http://www.tandfonline.com/loi/iphb202017-09-30hb2016AnatomyBiochemistr