Faculty of Health Sciences
School of Medicine
Department of Pharmacology
Selected Highlights from Research Findings
An in vitro study was conducted to determine the potential beneficial effect of selected African herbal remedies used for the treatment of neurodegenerative diseases, by assessing various endpoints. It was determined that several plants showed good inhibition of acetylcholinesterase, had good antioxidant activity and were able to reduce the effect of ˙-amyloid on neuroblastoma (SH-SY5Y) cells. The most promising plant, Boophane disticha, was selected for isolation and characterization of active compounds. Two compounds; a crinine alkaloid and a cycloartane triterpene, which are novel to the plant were isolated. Although the crinine alkaloid retained its acetylcholinesterase inhibitory activity it was found to be toxic to the SH-SY5Y cells. Quantitative structure activity relationship studies will be carried out to reduce the toxicity and improve the activity of the compound to undergo further investigation into the development as a pharmaceutical drug.
A PhD project entitled: “Development of an in vitro mechanistic toxicity screening model using cultured hepatocytes” was aimed at setting up a robust, multiparametric, cell-based hepatotoxicity assay that is conducive to high-throughput screening of compounds. The developed method assessed a number of cellular endpoints using a single 96-well microplate including: cell viability, phase I metabolism, oxidative and mitochondrial homoeostasis and mode of cell death. Results showed that the method allows for rapid accumulation of data, which is reproducible and cost-effective. Furthermore, the method generates multiparametric results, which are significantly comparable since they were obtained under the same experimental conditions. This, coupled with the fact that the cells are of human origin, may add to the efficacy of the developed procedure in terms of predicting in vivo hepatotoxicity. Due to the lack of preclinical in vitro screening for determination of the intrinsic hepatotoxicity of candidate drugs, there is potential for marketing this type of procedure to aid pharmaceutical research and development groups in lead compound selection and optimization.
Contact person: Prof OBW Greeff.
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