Browsing by Author "Jansen van Rensburg, Zune"

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    Identification of components of turmeric as potential therapeutic agents to slow the progression of neurodegeneration in Parkinson’s disease
    (Stellenbosch : Stellenbosch University, 2022-04) Jansen van Rensburg, Zune; Bardien, Soraya; Kenyon, Colin; Abrahams, Shameemah; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: Parkinson’s disease (PD) is a neurological disorder associated with severe loss of dopaminergic neurons in the substantia nigra. These neurons are particularly vulnerable due to increased iron and decreased antioxidant levels with aging, constant exposure to reactive oxygen species (ROS), and the presence of neurotoxic compounds. A literature review was compiled and published, in which we postulate that ROS, iron, alpha-synuclein protein (α-syn), and neuromelanin form a toxic feedback loop in individuals with PD. This feedback loop is theorised to be an early trigger culminating in neuronal death and subsequent spread of the disease to neighbouring neurons. Consequently, antioxidants and iron-chelators may be important therapeutic agents to target the accumulated ROS and iron in these neurons. Turmeric is an attractive therapeutic candidate since it has well-established antioxidant properties and may chelate iron. This study aimed to determine which components of turmeric have strong antioxidant and iron-chelating properties that could potentially protect against dopaminergic neuronal degeneration in PD. A crude extract was obtained from purchased turmeric using Soxhlet extraction. Subsequently, the crude extract was separated into different compounds using thin-layer chromatography (TLC). Mass spectrometry (MS) was used to identify the eluted compounds and a selected number of compounds were further analysed with liquid chromatography-mass spectrometry (LCMS). After identifying the compounds, four were chosen to test their total antioxidant capacity and iron chelation ability by comparing these compounds to Trolox (a known antioxidant) and ethylenediaminetetraacetic acid (EDTA) (a strong iron chelator), respectively. Finally, a human neuronal cell line, SH-SY5Y, was used to evaluate the effect of the extracted compounds on cell viability, through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We successfully obtained a crude extract from turmeric powder after Soxhlet extraction. A total of 34 bands were initially eluted from the TLC plate, with the experiment performed in duplicate. After MS, only 15 of the 34 samples had identifiable compounds. Through LCMS, four compounds were identified with confidence namely bis-demethoxycurcumin, demethoxycurcumin, curcumin, and aromatic (ar)-turmerone. The antioxidant assays showed that curcumin had the strongest antioxidant activity while ar-turmerone had the weakest. Analysis of the iron-chelating activity of these compounds found contradictory results. However, with spectrophotometric observation and a commercially validated kit, the curcuminoids were shown to have strong iron-chelation potential. Unexpectedly, ar-turmerone also showed iron-chelation potential albeit to a lesser extent compared to the curcuminoids. The exploratory analysis with the SH-SY5Y cells showed that bis-demethoxycurcumin increased cell viability by 152%, while ar-turmerone decreased it by 73.5%, versus the vehicle control. These promising findings warrant further study using more targeted techniques. Identifying new therapies for PD is of utmost importance since the current treatments only treat the symptoms and do not address the pathobiology of neuronal loss. Natural compounds extracted from plants may be particularly useful for the design of new treatment modalities since they may be more cost- effective and have fewer side effects than synthetic medicines.