The acquired immunodeficiency syndrome (AIDS) in humans, which is caused by the human immunodeficiency virus type 1 (HIV-1) remains among the leading causes of death worldwide. Although HAART has reduced HIV mortality significantly, adhering to the recommended drug schemes, significant toxicities experienced by treated patients, and the high mutation rate of the virus that seem to easily circumvent the action of these drugs emphasize the need for alternative treatment strategies. Medicinal plants are a good source for the discovery of novel antimicrobial chemotherapeutic agents. Reverse transcription is the most essential step for viral replication to succeed successfully. This makes reverse transcriptase the prime target for antiviral therapy against HIV. Emphasis was placed on the discovery of plants with inhibitory activity against HIV-1 reverse transcriptase. Crude extracts from the active plant(s) was screened in vitro for their ability to suppress HIV replication in suitable cell systems. The potential of isolating and identifying the active principle(s) was also investigated. Crude extracts from different parts of Gunnera perpensa showed similar amounts of inhibition: aqueous extracts (97% „b 0.110%SD), methanol/chloroform extracts (94% „b 2.374%SD), rhizome extracts (96% „b 0.475%SD), stem extracts (94% „b 3.723%SD), leaf extracts (96% „b 1.097% SD). Crude extracts were found to be significantly (P„T0.027) non-toxic to CEM.NKR.CCR5 cells and PBMCs at 5 ƒÝg/ml. In acutely infected CEM.NKR.CCR5 cells, acutely infected PBMCs, and chronically infected PBMCs Gunnera perpensa extracts did not significantly (P>0.05) increase cell viability or reduced HIV core protein content, over 4 days. The in vitro test did therefore not reflect the findings with the reverse transcriptase assay. Activity-guided fractionations of Gunnera perpensa rhizome extract lead to the collection of a significantly active fraction. NMR studies revealed the presence of an epimeric mixture of glucose ¡§contaminants¡¨ in this active fraction. The presence of these ¡§contaminants¡¨ concealed the true structure of the active principle. Gunnera perpensa was identified as containing a potential active principle that significantly inhibits recombinant HIV reverse transcriptase. Unfortunately, in vitro experiments could not confirm this finding. The identity and structure of the active principle remains unidentified. Future studies will be concerned with in vitro antiviral studies of the pure active principle. Furthermore, preliminary tests indicated that some of the original collection of crude extracts had anti-bacterial and anti-malarial activities. These findings can be investigated in future. / Dr. D. Meyer
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:6895 |
| Date | 06 May 2008 |
| Creators | Basson, Adriaan Erasmus |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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