Karen du Toit

The chemical structures, plant origins, ethnobotany and biological activities of homoisoflavanones

This work reviews the four basic structural types of homoisoflavanones. The relationships between the various structures of homoisoflavanones and their plant origins, ethnobotany and biological activities are put into perspective.

An investigation of the antimicrobial and anti-inflammatory activities of crocodile oil.

ETHNOPHARMACOLOGICAL RELEVANCE Crocodile oil has been used by traditional practitioners world-wide to treat microbial infections and inflammatory conditions. However, the scientific rationale behind its use is not completely understood. This study provides an updated fatty acid profile and novel scientific evidence of the antimicrobial and anti-inflammatory properties of crocodile oil, obtained from the Nile crocodile (Crocodylus niloticus), justifying its use by traditional healers. MATERIALS AND METHODS The fatty acid content of the oil was determined by gas chromatography and the major fatty acids were identified. A microplate method was used to assess activity of the oil against Staphylococcus aureus, Klebsiella pneumoniae and Candida albicans. The anti-inflammatory activity of the oil was assessed by oral administration and topical application, utilising a mouse model of acute croton oil-induced contact dermatitis. RESULTS Sixteen fatty acids were identified with oleic, palmitic and linoleic acid being the major components of the oil. The optimal activity of the oil against the bacteria and fungus was obtained with 15% and 6% (w/v) oil respectively. No significant selectivity was observed against the bacterial species, but Candida albicans was more susceptible. The anti-inflammatory assays showed optimal activity at 3h after the oral administration of oil (60.8±5.5%) and at 12h after topical application (57.5±5.9%). This suggested a short duration of action when the oil was orally administered, and a longer duration of action when it was topically applied. CONCLUSIONS Subsequent studies may be directed towards the investigation of the mechanisms of action of the antimicrobial and anti-inflammatory activities of crocodile oil and its fatty acids.

Experimental and theoretical studies of a naturally occurring non-oligomeric steroidal supramolecular zipper

Methanol extraction of the bulbs of Ornithogalum tenuifolium afforded a novel crystalline steroidal sapogenin (25R)-5β-spirostane-1β,3α-diol (compound 1). The structure and stereochemistry, but not the enantiomer, of this compound was unambiguously assigned using X-ray diffraction and multidimensional 1H and 13C NMR data. The crystal structure of 1 (monoclinic space group P21) is both novel and remarkable in that the extended lattice or “supramolecular” structure comprises an unusual one-dimensional hydrogen-bonded polymer with 21 symmetry (the polymer axis is co-linear with the b-axis of the unit cell). Each ladder-like hydrogen-bonded polymer stacks in an interlocking fashion with a neighbouring polymer along the c-axis of the unit cell. The self-recognition by hydrogen-bonding that leads to the formation of the polymer is characterized by discrete 10-membered supramolecular rings. Moreover, the steroid units of the one-dimensional polymer interlock perfectly to form a supramolecular zipper. The newly-discovered supramolecular synthon of the zipper has been elaborated on due to its possible use in crystal engineering applications. The supramolecular zipper system has also been simulated in vacuo using semi-empirical (AM1) quantum mechanics techniques, which correctly reproduce not only the experimental conformation but also the hydrogen-bonded extended structure of the compound. The simulations showed that formation of the supramolecular zipper structure of 1 most likely reflects charge-complementarity of its hydrogen-bonded hydroxy groups and that the electrostatically driven process is characterized by a favourable and cooperative in vacuo enthalpy of association. A further hallmark of the self-assembly of 1 was the lowering of the mean vibrational frequency of the hydrogen-bonded hydroxy groups upon formation of the zipper.

Anti-inflammatory activities of selected synthetic homoisoflavanones

Four homoisoflavanones of the 3-benzylidene-4-chromanone type, some of which were previously isolated from Caesalpinia pulcherrima, were synthesised to determine their anti-inflammatory activity and cytotoxicity. A range of four different homoisoflavanones (compounds 4a–4d) were synthesised from the corresponding substituted phenols.1H- and 13C-NMR data together with high-resolution mass spectroscopy data were employed to elucidate the structures. Anti-inflammatory activity was determined in mice with acute croton oil-induced auricular dermatitis. In vitro cytotoxicity was tested against a Chinese hamster ovarian cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Compound 4a exhibited a tendency to inhibit oedema in a dose-dependent manner after 3 and 6 h of treatment. Compounds 4b–4d also inhibited oedema, although a clear dose-response relationship was not observed. Compounds 4a–4c were found to be less cytotoxic than compound 4d. Compound 4b was the least cytotoxic. Compounds 4a–4d exhibited anti-inflammatory activity and varying levels of cytotoxicity.

The cytotoxic effects of Scilla nervosa (Burch.) Jessop (Hyacinthaceae) aqueous extract on cultured HepG2 cells

ETHNOPHARMACOLOGICAL RELEVANCE Bulbs of Scilla nervosa, a medicinal plant indigenous to Southern Africa, are traditionally used in aqueous decoctions to treat a diverse range of illnesses. The bulbs contain homoisoflavanones and stilbenoids. Little information is known about the plants toxicity on the liver, a major detoxifying organ. This study investigated the effects of an aqueous extract of the bulbs in cultured HepG2 liver cells, a model system for investigating the toxicity of xenobiotics. MATERIALS AND METHODS The concentration that reduced cell viability to 50% (IC(50)) after 24h treatment was derived. Potential mechanisms of toxicity using the IC(50) were investigated as changes in metabolic activity, apoptosis, oxidative damage and DNA fragmentation. In addition, cytochrome P450 3A4 (CYP3A4) activity, which is implicated in drug metabolism and interactions, was also assayed. RESULTS Cell viability decreased in a concentration-dependent manner and the IC(50) was determined as 0.03 mg/mL. Treating the cells at the IC(50) for 24h resulted in increased intracellular ATP levels, no significant change in phosphatidylserine externalisation, increased caspase-8 activity, decreased caspase-9 activity, no significant change in mitochondrial membrane potential, increased lipid peroxidation, evidence for genotoxicity as demonstrated by DNA fragmentation, and slightly induced CYP3A4 activity. CONCLUSION Results suggest that liver cells are sensitive to an aqueous extract of the bulbs and there is an increased potential to induce apoptosis, oxidative stress and genotoxicity in vitro.

Patents and the quality, safety and efficacy of medicines.

The impact of patent circumvention potentially has serious implications with regard to medicine quality, safety and efficacy, even if it was intended to improve accessibility and affordability of medicines. Companies should therefore conduct adequate research in order to understand the effect of patent circumvention on the quality, safety and efficacy of medicine.

Complementary medicines: When regulation results in revolution

Medicines have evolved over time and so has the realisation of the importance of quality control and regulatory processes. The regulatory practices include all the steps from the development and manufacture of the active ingredients until the medicines reach the consumer. The Medicines Control Council (MCC) is mandated to regulate medicines in South Africa. Complementary medicines were previously perceived to be unregulated, although the Medicines Act does not distinguish between allopathic and complementary medicine. As the era of unregulated complementary medicine ended, the requirements in terms of dossier content left many role-players at odds. However, the MCC has a mandate to ensure that the registration of a medicine is in the interest of the public and that complementary medicine is manufactured in a facility adhering to good manufacturing practice, according to which efficacy and safety are supported by reliable data with a known shelf-life.

The Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae to Naturally Derived Selected Classes of Flavonoids

The emergence of multi-drug resistant organisms has increasingly become a global public health issue. Rational and appropriate uses of antibiotics as well as strict infection control measurements are recommended in order to reduce the emergence of antibiotic resistant bacteria (Tseng et al., 2011). The complexity in treating multi-drug resistant infections has led to an increase in the search for novel and effective antibiotics, especially structures originating from natural products. Promising molecules could serve as lead compounds to be developed and researched further.