Browsing by Author "Du Toit, Karen."

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A phytochemical investigation of members of the hyacinthaceae family and biological screening of homoisoflavanones and structurally related compounds.
(2004) Du Toit, Karen.; Drewes, Siegfried Ernst.; Mulholland, Dulcie Aca.
The Hyacinthaceae family is richly represented in southern Africa. Of the five subfamilies, three are found in southern Africa. These are the Urgineoideae (URG), Ornithogaloideae (ORN) and the Hyacinthoideae (HYA). The overview of Pfosser and Speta (1999), revealed chemotaxonomic trends at a subfamily level for the Hyacinthaceae family of the Flora of southern Africa region. Homoisoflavanones were found to define the Hyacinthoideae subfamily whilst the Ornithogaloideae subfamily and the Urgineoideae subfamily are defined by steroidal compounds namely, cholestane glycosides and bufadienolide glycosides respectively. Representatives of all three subfamilies were investigated phytochemically. From Eucomis comosa (HYA), five homoisoflavanones were isolated. Omithogalum tenuifolium (ORN) contained a spirostanol saponin of which the crystals were amenable to X-ray analysis. Evidence of a novel stereoisomer was obtained. Extraction of the bulbs of Galtonia princeps (ORN) led to the isolation of two cholestane glycosides, one known and one novel, and a homoisoflavanone. Two novel bufadienolides were isolated from Urginea Iydenburgensis (URG). Structures were elucidated on the basis of spectroscopic data and chemical evidences. Homoisoflavanones and related compounds were then screened for antibacterial and anti-inflammatory activity. Several compounds showed antibacterial activity against Staphylococcus aureus, a gram-positive bacteria. Inhibition of the inflammatory process in microsomal cells was first evaluated, followed by screening of specific inhibition of cyclooxygenase enzymes. These are membrane-associated enzymes occurring in different isoforms. High levels of anti-inflammatory activity were detected especially in microsomal cells. This biological information made it possible to rationalize the ethnomedicinal use of some of the plants from which the compounds were isolated. 15 Biological screening was followed by a computer-based quantitative structureactivity relationship (QSAR) study. This study produced five equations with significant prediction value of anti-inflammatory and antibacterial activity for homoisoflavanones and related compounds. The derived models also provided valuable parameter guidelines of those properties influencing the antiinflammatory and antimicrobial activity of the studied compounds.
Synthesis and biological activities of natural homoisoflavanones.
(2011) Shaikh, Mahidansha Mahiboob.; Du Toit, Karen.; Kruger, Hendrik Gerhardus.
Plants have formed the foundation of traditional medicine systems throughout the world for thousands of years and continue to provide mankind with new remedies for various ailments. A large portion of the black South African population still depends on medicinal plants as primary health care due to its affordability, accessibility and cultural importance. These medicinal plants need to be investigated since new lead compounds are often found in nature. Homoisoflavanones isolated from South African and Indian plants were found to exhibit anti inflammatory activities although the mechanism of action has not yet been determined. A few reports on the anti fungal activities of these compounds were also found. Four new and three known homoisoflavanones of the 3-benzylidene-4-chromanone type were synthesized and tested for anti-inflammatory and antifungal activities. Two novel intermediates were also synthesised. Enantiomers of a homoisoflavanone of the 3-benzyl-4- chromanone types were also synthesized from the corresponding 3,5-dimethoxy phenol via 4- chromanone in six steps. This is the first report of the synthesis of an enantiomerically pure homoisoflavanone compound together with its opposite isomer. The enantiomers and racemate were tested for anti-inflammatory activity. All the synthesized homoisoflavanones were screened for cytotoxicity. The structures of these homoisoflavanones were elucidated by NMR spectroscopy along with HRMS data. The crystal structure of a homoisoflavanone with anti-inflammatory and antifungal activity is reported. The anti-inflammatory activity of the homoisoflavanones was determined in an acute croton oil-induced auricular dermatitis mouse model. The antifungal activity was performed in vitro against a Candida albicans strain. Compounds were tested for cytotoxicity against a Chinese Hamster Ovarian (CHO) cell line using the 3-(4,5-dimethylthiazol-2-yl)-3,5- diphenyltetrazoliumbromide (MTT) assay. In conclusion, the synthetic homoisoflavanones showed anti-inflammatory as well as antifungal activity. Some of the compounds showed anti-inflammatory activity comparable to that of the commercially available diclofenac.
The toxicological properties of Scilla nervosa (Burch.) Jessop (Hyacinthaceae) in cultured HepG2 liver cells.
(2011) Pillay, Prishania.; Bodenstein, Johannes.; Chuturgoon, Anil Amichund.; Du Toit, Karen.
Background and Aims of Study. Scilla nervosa is a member of the Hyacinthaceae plant family that has been naturalised in the grasslands of Southern Africa. The bulbs are traditionally used to treat a variety of ailments. For example, the Zulu people use aqueous decoctions of the bulbs as analgesics in the treatment of rheumatic fever, crushed bulbs are used by the Sotho people as laxatives and the Tswana people use cooked bulbs to treat infertility in women as well as cold aqueous extracts to treat infections. It was recently demonstrated in our laboratory that extracts prepared from the bulbs possess potent anti-inflammatory properties, and this may therefore provide a rationale for the traditional use of the plant as an analgesic. Several studies have demonstrated that the bulbs contain homoisoflavanones and stilbenoids that could be responsible for their therapeutic effects. Although the plant has diverse medicinal applications, and despite it being recognised as a poisonous species particularly in livestock, little is known about its toxicity in human liver cells. The objectives of this study were therefore to investigate the potential toxicity of the bulbs on the liver, a major detoxifying organ. A human liver cell line was treated with an aqueous extract of the bulbs to investigate (1) cell viability, (2) potential mechanisms of cytotoxicity, (3) DNA integrity, and (4) changes in the cytochrome P450 enzyme activity. Materials and Methods. This study was conducted on the cultured HepG2 human hepatocellular carcinoma cell line, a model system to investigate the cytotoxicity of xenobiotics. The viability of cultured HepG2 liver cells in the presence of varying concentrations of an aqueous extract of the bulbs was determined after 24 hours treatment, and the concentration that reduced viability to 50% (IC50) was derived. Potential mechanisms of cytotoxicity at the IC50 were investigated. These included changes in metabolic activity (intracellular adenosine triphosphate (ATP) quantification), apoptosis induction (phosphatidylserine (PS) externalisation, caspase-8 and -9 induction and changes in mitochondrial membrane potential), and oxidative damage via free radical formation (lipid peroxidation). Genotoxicity was investigated by determining changes in DNA integrity (DNA fragmentation). The ability of the extract to stimulate or {¹ Du Toit, K., Kweyama, A., Bodenstein, J. 2011. Anti-inflammatory and antimicrobial profiles of Scilla nervosa (Burch.) Jessop (Hyacinthaceae). South African Journal of Science, 107:96-100.} inhibit enzymes commonly involved with drug metabolism was investigated by determining cytochrome P450 3A4 (CYP3A4) activity. Results Cell-viability decreased in a concentration-dependent manner and the IC50 was determined as 0.03 mg/ml. Treating the cells at the IC50 resulted in (1) a 1.2-fold increase in intracellular ATP levels, (2) no significant change in PS externalisation, (3) a 1.3-fold increase in caspase-8 activity, (4) a 1.1-fold decrease in caspase-9 activity, (5) no significant change in mitochondrial membrane potential, (6) a 1.9-fold increase in lipid peroxidation, (7) evidence for genotoxicity as demonstrated by DNA fragmentation, and (8) no evidence of changes in CYP3A4 activity. Conclusion. Results suggest that HepG2 liver cells are sensitive to an aqueous extract of the bulbs of S. nervosa. The extract has the potential to (1) induce apoptosis, (2) increase oxidative stress and (3) cause genotoxicity in vitro. peroxidation, genotoxicity