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dc.contributor.authorWambua, Mukavi Justus
dc.date.accessioned2021-01-29T11:38:07Z
dc.date.available2021-01-29T11:38:07Z
dc.date.issued2020-12-11
dc.identifier.urihttp://repository.embuni.ac.ke/handle/embuni/3721
dc.descriptionThesisen_US
dc.description.abstractCancer has become a key public health affliction worldwide. Recent studies have shown that genetic factors cause only 5–10% of all human cancers, while the rest are caused by lifestyle. Epidemiological and clinical studies have shown that chronic inflammatory diseases predispose individuals to various types of cancer. An estimated 20 % of all cancer related deaths globally arise from primary infections and inflammation. Current treatments for cancer include radiotherapy, chemotherapy, surgery, hormone, immune and targeted therapies. However, the efficacy of these treatments is constrained by their unexpected detrimental effects on other non-target tissues, development of multi-drug resistant cancer cell lines and high cost. Medicinal plants are increasingly attracting attention of researchers as a source of complementary and alternative therapies to mitigate cancer morbidity and mortality. Plants have been reported to contain bioactive phytochemicals with anti-infective properties against chronic diseases, including inflammation and cancer. In the current study the air-dried roots bark and leaves of Fagaropsis angolensis were pulverized into fine powders. The plant materials were then exhaustively extracted with 50% CH3OH in CH2Cl2 (v/v) at room temperature by cold solvent percolation. Separation was carried out using column chromatography on silica gel as the stationary matrix and eluted with gradients of n-hexane, EtOAc and MeOH. The resultant fractions were then purified using finer silica gel by recurrent column chromatography, Sephadex LH 20 and Chromatotron to afford a total of five compounds including two new norhopane derivatives; 3β,6β,22-trihydroxy-7β,11α-di[(4-hydroxybenzoyl)oxy]21αH-24-norhopa-4(23)-ene (42) and 3β,6β,22-trihydroxy-7β-[(4- hydroxybenzoyl)oxy]-21αH-24-norhopa-4(23)-ene (43) together with the known norhopane, 3β,6β,11α-trihydroxy-7β-[(4-hydroxybenzoyl)oxy]-24-norhopa- 4(23),17(21)-diene (44) and a norneohopane, (21α-H)-24-norneohopa-4(23), 22(29)diene-3β,6β,7β-triol 7-caffeate (30) from the root bark. The leaves afforded a reported flavone, tachrosin (45). Their structure elucidation was achieved by detailed 1D and 2D NMR, HRESI-MS, FT-IR and UV spectra for the newly described compounds and by comparison of these data with those of correlated compounds in the published literature. Resazurin reduction assay was used to evaluate the cytotoxicity of compound 46, with doxorubicin as reference anticancer drug. Compound 46 displayed minimal activity since the cell viability was more than 70 % against drug sensitive CCRF-CEM. Owing to the risk associated with chronic inflammation to initiation, promotion and progression of carcinogenesis, compounds 42 – 45 were assessed for their anti-inflammatory activity by quantifying the levels of cytokines Interleukin-1β (IL-1β), Interleukin-2 (IL-2), Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMCs). All tested compounds decreased secretion of IL-1β and TNF-α. Compounds 43 and 45 clearly decreased secretion of IL-2, GM-CSF and TNF-α in comparison with the reference drug ibuprofen. The findings from this study revealed that F. angolensis contains significant amounts of hopane-type triterpenoid derivatives with potential to downregulate pro-inflammatory biomarkers and further provide a scientific rationale for using the plant in Kenyan folk medicine as anti-pain solution.en_US
dc.language.isoenen_US
dc.publisherUniversity of Embuen_US
dc.titleAnti-Cancer and Anti-Inflammatory Secondary Metabolites of Fagaropsis Angolensis (Engl.) H.M. Gardneren_US
dc.typeThesisen_US


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