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Antimalarial activity of hypoxis colchicifolia, bak, mimusops caffra, E. Mey. ex A.DC and mimusops obtusifolia, lam from South Africa

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dc.contributor.advisor Opoku, A.R.
dc.contributor.advisor Shonhai, A.
dc.contributor.advisor Shode, O.O.O.
dc.contributor.author Simelane, Mthokozisi Blessing Cedric
dc.date.accessioned 2014-07-07T07:56:27Z
dc.date.available 2014-07-07T07:56:27Z
dc.date.issued 2014
dc.identifier.uri http://hdl.handle.net/10530/1332
dc.description Dissertation submitted to the Department of Biochemistry and Microbiology, in the Faculty of Science and Agriculture, in fulfillment of the requirements for Doctoral (PhD) degree in Biochemistry at the University of Zululand, South Africa, 2014. en_US
dc.description.abstract Malaria is one of the major health problems of today, more so since the parasite has become resistant to the currently used drugs. There is a need for research into new drugs from medicinal plant species which are used by local traditional healers for the treatment of malaria. Mimusops caffra, E.Mey. ex A.DC, Mimusops obtusifolia, Lam (both members of Sapotaceae family) and Hypoxis colchicifolia, Bak are used by traditional healers in Zululand to manage malaria. In this study, the plants were separately extracted exhaustively with methanol, ethyl acetate, hexane and dichloromethane (DCM). The crude extracts were screened for antioxidant, antipyretic, and antimalarial activity. The antioxidant activity of the methanol extracts was determined by measuring the decrease in the colour of an oxidative system in the presence and absence of the extract. The various antioxidant activities tested include free radical scavenging, Fe2+ chelating, reducing power, and total antioxidant capacity. Yeast induced pyrexia was used to evaluate the antipyretic activity of the plant extracts. In vitro antimalarial activity of the extracts was investigated against the chloroquine sensitive (CQS) strain of Plasmodium falciparum (D10) and the in vivo antiplasmodial activity was done against Plasmodium berghei. The most active in vitro antiplasmodial crude extracts were subjected to isolation, purification and characterization of the active components using column chromatographic techniques. The triterpenes isolated were confirmed using Nuclear Magnetic Resonance (NMR) techniques with the application of 2D-NMR (1H-1H, 13C, DEPT, COSY, HMQC, HMBC and NOESY) and infrared (IR). The preliminary phytochemical analysis of plants’ extracts revealed the presence mainly of saponins, tannins, alkaloids and flavonoids. Methanol extracts of the plants exhibited strong scavenging of 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) and 3- ethylbenzothiazoline-6-sulfonate (ABTS) radicals, but showed poor (< 50%) radical scavenging of nitric oxide, superoxide and hydroxyl radicals. The DCM extract of the leaves of M. caffra and the ethyl acetate extract of the bark of M. obtusifolia exhibited antimalarial activity against the chloroquine sensitive (CQS) strain of Plasmodium falciparum (D10). The leaf extracts of M. caffra exhibited higher activity (IC50=2.14 μg/ml) compared to the extracts of M. obtusifolia (IC50=32.5 μg/ml). The pentacyclic tritepenoid (PTCs) ursolic acid isolated from the leaves of M. caffra was most active (IC50 = 6.8 μg/mL) in comparison to taraxerol and Sawamilletin isolated from the stem bark of M. obtusifolia with IC50 of > 100. Chemical modification of the ursolic acid to 3β-acetylursolic acid greatly enhanced (72%) its anti-plasmodial activity. The 3β-acetylursolic acid reduced parasitaemia against Plasmodium berghei by 94.01% in in vivo studies in mice. An attempt to elucidate the possible mechanism of action for the active compound was carried out. 3β-acetylursolic acid prevented the aggregation of MDH in vitro but did not prevent the expression of PfHsp 70 in E.coli XL1 blue cells. However, it showed PfHsp 70 ATPase activity with the specific activity of 65 (amount of phosphate released 73.83 nmolPi/min/mg). The cytotoxicity of 3β-acetylursolic acid (IC50) to two human cell lines (HEK293 and HepG2) was 366.00 μg/ml and 566.09 μg/mL, respectively. The results validate the use of these plants in folk medicine. en_US
dc.description.sponsorship University of Zululand and National Research Foundation (NRF) en_US
dc.language.iso en en_US
dc.publisher University of Zululand en_US
dc.subject Malaria -- treatment of en_US
dc.subject Malaria -- traditional healers en_US
dc.title Antimalarial activity of hypoxis colchicifolia, bak, mimusops caffra, E. Mey. ex A.DC and mimusops obtusifolia, lam from South Africa en_US
dc.type Thesis en_US

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