Identification of components of turmeric as potential therapeutic agents to slow the progression of neurodegeneration in Parkinson’s disease

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dc.contributor.advisorBardien, Sorayaen_ZA
dc.contributor.advisorKenyon, Colinen_ZA
dc.contributor.advisorAbrahams, Shameemahen_ZA
dc.contributor.authorJansen van Rensburg, Zuneen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.en_ZA
dc.date.accessioned2022-02-18T16:46:56Z
dc.date.accessioned2022-04-29T09:25:35Z
dc.date.available2022-02-18T16:46:56Z
dc.date.available2022-04-29T09:25:35Z
dc.date.issued2022-04
dc.descriptionThesis (MSc)--Stellenbosch University, 2022.en_ZA
dc.description.abstractENGLISH 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.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Parkinson se siekte (PS) is ‘n neurologiese afwyking wat geassosieer word met ernstige verlies van dopaminerge neurone in die substantia nigra. Hierdie neurone is kwesbaar as gevolg van verhoogde yster en verlaagde antioksidant vlakke met veroudering, konstante blootstelling aan reaktiewe suurstofspesies (RSS) en neurotoksiese verbindings. ‘n Literatuurstudie was gepubliseer, wat blyk dat RSS, yster, alfa-sinuklein (α-syn) en neuromelanien 'n toksiese terugvoer in PS-individue vorm. Hierdie terugvoer veroorsaak neuronale dood en die siekte versprei verder na aangrensende neurone. Antioksidante en ystercheleerders kan as belangrike terapeutiese middels beskou word om die opgehoopte RSS en yster in dopaminerge neurone te verminder. Borrie is ‘n geskikte terapeutiese kandidaat aangesien dit gevestigde antioksidante eienskappe beskik en mag dalk yster verbind. Die doel van hierdie studie is om vas te stel watter borrie komponente antioksidant- en ysterverbindings eienskappe toon, wat die moontlike afbraak van dopaminerge neurone in PS kan verhoed. ‘n Ru-ekstrak was met behulp van ‘n Soxhlet-ekstrakie uit borrie onttrek. Komponente was daarna met behulp van dunlaagchromatografie (DLG) uit die ru-ekstrak geëkstraheer. Massaspektrometrie (MS) was gebruik om die geëlueerde komponente te identifiseer. ‘n Geselekteerde aantal verbindings is verder ontleed deur vloeistofchromatografie massaspektrometrie (VCMS). Nadat die komponente geïdentifiseer was, was vier gekies om hulle antioksidant kapasiteit en ysterchelerings vermoë te bepaal. Hierdie komponente was onderskeidelik met Trolox (‘n sintetiese analoog van vitamien E) en etileendiamientetra-asynsuur (EDTA) (‘n sterk ysterchelaat vormer) vergelyk. Laastens is die menslike neuronale sellyn, SH-SY5Y, gebruik om die effek van die geskeide verbindings op dopaminerge neurone te evalueer, deur middel van 'n 3-(4,5-dimetieltiasool-2-yl)-2,5-difenieltetrazoliumbromied (MTT) toets. ‘n Ru-ekstrak was suksesvol verkry uit die borriepoeier na die Soxhlet-ekstraksie. ‘n Totaal van 34 bande was aanvanklik van die DLG-plaat geëlueer. Die eksperiment was in duplikaat uitgevoer. Na MS het slegs 15 van die 34 bande identifiseerbare komponente gehad. Deur VCMS was vier komponente met vertroue geïdentifiseer, naamlik bisdemetoksikurkumien, demetoksikurkumien, kurkumien, en aromatiese (ar)- turmeroon. Kurkumien het merwaardige antioksidant kapasiteit getoon, terwyl ar-termeroon swak was. Deur spektrofotometriese waarnemings en ‘n kommersiële bekragtigde stel, was daar getoon dat die kurkuminoïede sterk ysterchelaat vermoëns het. Die ar-turmeroon het ook ysterchelaat vermoëns getoon, alhoewel in ‘n mindere mate as die kurkuminoïede. Die proef eksperiment met die SH-SY5Y-selle het getoon dat bisdemetoksikurkumien sellewensvatbaarheid met 152% verhoog het, terwyl ar-turmeroon dit met 73.5% verlaag het, teenoor die voertuigkontrole. Hierdie belowende bevindinge regverdig verdere studie deur meer gespesialiseerde en geteikende tegnieke te gebruik. Die identifisering van nuwe terapieë vir PS is egter van uiterste belang aangesien die huidige terapieë slegs die simptome behandel en nie die patobiologie van neuronale verlies aanspreek nie. Plantaardige verbindings kan veral nuttig wees vir die ontwerp van nuwe behandelings modaliteite aangesien dit meer koste-effektief is en oor minder newe-effekte beskik as sintetiese medisyne.af_ZA
dc.description.versionMastersen_ZA
dc.format.extent154 pagesen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/124671
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subjectParkinson's diseaseen_ZA
dc.subjectDopaminergic neuronen_ZA
dc.subjectAntioxidanten_ZA
dc.subjectIronen_ZA
dc.subjectTurmericen_ZA
dc.subjectCurcuminen_ZA
dc.subjectDopamine oxidationen_ZA
dc.subjectUCTDen_ZA
dc.titleIdentification of components of turmeric as potential therapeutic agents to slow the progression of neurodegeneration in Parkinson’s diseaseen_ZA
dc.typeThesisen_ZA
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