Studies towards the development of African phytomedicines from Combretum apiculatum and Galenia africana

dc.contributor.advisorMarston, Andrew
dc.contributor.advisorBonnet, Susan L.
dc.contributor.advisorVan der Westhiuzen, Jan H.
dc.contributor.authorPhungula, Khanya Valentine
dc.date.accessioned2015-11-18T13:40:07Z
dc.date.available2015-11-18T13:40:07Z
dc.date.issued2015-01
dc.description.abstractNearly 80% of the world population use traditional medicine, mainly medicinal plants, to treat diseases and ailments. In developing countries and rural communities, the use of traditional medicine is a valuable resource and a necessity and provides a real alternative for primary health care systems. These have commonly not been investigated for safety and efficacy and are not used in standardized doses. The active ingredients are often not known. The need thus exist to develop standardized phytomedicines. In this dissertation we investigated the scientific experimental techniques required during the process to develop acceptable, standardized, efficacious and safe phytomedicines from South African Indigenous knowledge and African Traditional Medicine. Due to time and other constraints during this MSc dissertation we could not work on a single plant and disease but used different plants to investigate the different aspects. The following are important:: - Identification of plants and extracts extracts that can be used to develop phytomedicines. - Establishment of safety and toxicity of a plant extract or isolated pure bioactive compounds - Determination of efficacy - Quality control In Chapter 1 we gave a brief introduction into the development of phytomedicines In Chapter 2 we performed an ethnobotanical investigation to identify plants used by traditional health practitioners (THPs) to treat tuberculosis in the districts of Mangaung Metro, Thabo Mofutsanyana and Lejweleputswa in the Free State province, South Africa. A total of 37 THPs were interviewed using guided questionnaires. The THPs reported 19 plant species used to treat tuberculosis, of which Artemisia afra was the most frequently administered. The practitioners formulate and dispense their own recipes, most frequently using the tubers, roots and leaves of plants, but there was low consensus among the THPs as to which plants (or mixture of plants) are most efficacious. We concluded that the three plants most frequently administered, A. afra and H. caespititium (both Asteraceae), and L. lanceolata (Fabaceae), are candidates for further phytochemical investigation into their antimycobacterial and toxic properties, and to determine the efficacy of extracts and isolated compounds. In Chapter 3 we investigated toxicity issues by assessment of potentially cardiotoxic properties of extracts from traditionally used medicinal plants. hERG (human Ether-à-go-go Related Gene) is a gene that encodes the pore-forming α-subunit of a voltage-gated potassium K+ channel expressed in the heart and nervous tissue. Mutations in hERG can lead to partial or complete loss of function, and may cause cardiac arrhythmia that can degenerate into ventricular fibrillation, leading to sudden death. We investigated the effect of plant extracts on ion channels expressed in heterologous Xenopus laevis oocytes by means of the two microelectrode voltage-clamp technique. The DCM and MeOH extracts from 129 plant species were screened on Xenopus laevis oocytes for their potential cardiotoxic risk. Plant extracts that reduced the peak tail current by ≥30% hERG were considered positive hERG channel blockers. Plant extracts showing an inhibition between 30-60% at a concentration of 100 ug/mL were identified. In Chapter 4, a retrospective treatment outcomes based study was performed to investigate the efficacy of the plant preparations used by the population in the Thaba ‘Nchu district in the Free State, South Africa, for the treatment of diarrhoea. Thirty two patients were interviewed using guided questionnaires. Thirteen plant species were reported, of which Xysmalobium undulatum and Punica granatum were the most frequently used plant species. The majority of the patients (94.7%) had a successful treatment outcome even though the efficacy of the remedies varied. In Chapter 5, phytochemical investigation of two medicinal plants, Galenia africana L. and Combretum apiculatum Subsp. apiculatum, led to the isolation of five known compounds, four of which were isolated from the plants for the first time. The isolated compounds were identified as 7,8-dimethoxy-2-phenyl-4H-chromen-4-one (A), 6,7- dimethoxy-2-phenyl-4H-chromen-4-one (B), 8-phenyl-6H-[1,3]dioxolo[4,5-h]chromen-6-one (C), 5,7-dihydroxy-2-phenyl-3-((3S,4S,5S,6R)-3,4,5-trihydroxy-6-methyltetra-hydro-2H- pyran-2-yloxy)-4H-chromen-4-one (D) and 5-hydroxy-7-methoxy-2-phenylchroman-4-one (E) via NMR spectroscopy and ESI mass spectrometry. It is important for quality control to identify the active molecules responsible for the medicinal properties of a plant to ensure that these molecules occur in the same concentration in all phytomedicine batches. In Chapter 6, the extracts and pure isolates were subjected to in-house TLC bioassays (antioxidant and inhibition of acetylcholinesterase), and antimicrobial and antimycobacterium testing (performed at the University of the Witwatersrand). G. africana and C. apiculatum have been used traditionally to treat infectious diseases, and our phytopharmacological study on the two plants has confirmed these practices. We found that, - G. africana exhibits relatively low radical scavenging activity for the DCM extract and no activity for the MeOH extract, while both the seed and leave MeOH extracts from C. apiculatum displayed significant antioxidant activity - The DCM extract of G. africana and isolated compounds A and C showed acetylcholine esterase (AChE) inhibition - The DCM extract of G. africana showed significant activity against all four pathogens with the best activity observed against C. neoformans. - The highest activity against E. faecalis and K. pneumonia was from the MeOH crude extract of the seeds of C. apiculatum, and against C. neoformans the BuOH partition fraction from the seed extract - The seed and leave extracts of C. apiculatum and the partition fractions thereof all exhibited significant activity against M. smegmatis We have thus researched protocols to develop standardized phytomedicines from traditionally used plants.en_ZA
dc.identifier.urihttp://hdl.handle.net/11660/1673
dc.language.isoenen_ZA
dc.publisherUniversity of the Free Stateen_ZA
dc.rights.holderUniversity of the Free Stateen_ZA
dc.subjectDissertation (M.Sc. (Chemistry))--University of the Free State, 2015en_ZA
dc.subjectTraditional medicineen_ZA
dc.subjectCombretaceaeen_ZA
dc.subjectPrimary health careen_ZA
dc.subjectHerbs -- Therapeutic useen_ZA
dc.titleStudies towards the development of African phytomedicines from Combretum apiculatum and Galenia africanaen_ZA
dc.typeDissertationen_ZA
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