A dissertation submitted to the Faculty of Science under the School of
Molecular and Cell Biology, University of the Witwatersrand, Johannesburg,
in fulfilment of the requirements for the degree of Master in Science.
Johannesburg, June 2017. / In South Africa, the anti-HIV-1 activity of various indigenous plants has not been
studied extensively. Most of the phytochemical screening work has focused on
anti-cancer activity with less attention given to infectious diseases. A large
proportion of South Africans (70-80%) still rely on traditional medicines for
treatment of various ailments. And, therefore, there is a need to evaluate and
validate the effectiveness of the traditional medicines. The aim of this study was
to identify, screen, phytochemically characterize and isolate bioactive compounds
from a South African herbal extract that exhibit the best anti-HIV-1 activity.
Three extracts were prepared: an ethanol extract, a dereplicated ethanol extract
and an aqueous extract from a herbal concoction comprised of a mixture of six
plants. These herbal concoctions were investigated for anti-HIV-1 subtype C
activity.
Phytochemical profiling of the ethanol- and dereplicated ethanol- extracts from
the herbal concoctions showed the presence of intermediate polar compounds
(flavonoids, alkaloids, sugars and terpenes) for both extracts, while the aqueous
extract contained predominantly highly polar compounds.
Anti-HIV-1 screening of the three extracts showed that the ethanol and
dereplicated ethanol herbal- extracts had the best anti-reverse transcriptase
activity. The ethanol extract had mean IC50 values of 56.53, 53.96 and 55.39
μg/ml against MJ4, Du179 and CM9 HIV-1 subtypes C isolates, respectively. The
dereplicated ethanol extract had mean IC50 values of 51.87, 47.56 and 52.81
μg/ml against MJ4, Du179 and CM9 HIV-1 isolates, respectively. The aqueous
extract was inactive against HIV-1 activity.
Moreover, both the ethanol- and dereplicated ethanol- extracts showed activity
against HIV neutralization. The ethanol- and dereplicated ethanol- extracts had
mean IC50 values of 36.33 and 32.06 μg/ml, respectively. Furthermore, they also
potently neutralized Vesicular stomatitis virus (VSV) yielding mean IC50 values
of 24.91 and 20.82 μg/ml for ethanol- and dereplicated ethanol- extracts,
respectively. All extracts were inactive against Murine leukemia virus (MLV).
The isolation and phytochemical characterization of the bioactive compound(s)
was done by utilizing various chromatographic and spectroscopic methods. Four
homoisoflavanoids were isolated and tested for anti-HIV-1 subtype C activity.
Three compounds (1, 3a and 3b) were inactive while compound 2 was found to be
bioactive against HIV-1 reverse transcriptase (RT) and yielded mean IC50 values
of 7.23 ± 1.88, 12.83 ± 0.41 & 12.81 ± 0.10 μg/ml for MJ4, CM9 and Du179
HIV-1 subtype C isolates, respectively. Compound 2 had a mean CC50 value of
23.08 ± 0.1981 μg/ml against HEK293T cells.
Overall, the data suggested that ethanol- and dereplicated ethanol- herbal extracts
possess direct and indirect anti-HIV-1 activity. They possess a cocktail of
phytochemicals that can inhibit HIV-1 RT, HIV-1 entry. Furthermore, these
extracts possess phytochemicals that can lower the activation of inflammatory
responses during an infection and, hence, reduction in the number new cells
infected during the course of HIV-1 infection. Moreover, they possess
phytochemicals that have antioxidant activity which, in relation to HIV infection,
results in a boosted immune system response in order to ward off the virus. / MT 2017
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/23466 |
| Date | January 2017 |
| Creators | Hlatshwayo, Vincent Nkosinathi |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | Online resource (xix, 171 leaves), application/pdf |
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