Venereal diseases (VDs) are infections that are mainly transmitted through sexual intercourse and amongst these are gonorrhoea, syphilis, chlamydia and trichomoniasis. Gonorrhoea is the most commonly known VD and the widest spread contagious infection in the world. Out of 448 million cases of curable venereal infections, gonorrhoea represents 88 million cases and the rest are syphilis, chlamydia and trichomoniasis. Gonorrhoea has recently been rated as in the emergent multidrug resistance phase. Venereal diseases are amongst the major diseases ravaging many rural communities. People infected with these diseases are considered a disgrace in the community. Indigenous populations, for example the Vha-Venda people tend to use medicinal plants to treat these infectious diseases rather than using western medicines. Vha-Venda people have depended on medicinal plants for their health and survival for millenia. In order to validate and give scientific credence to the use of medicinal plants by the Vha-Venda people for venereal diseases, several pharmacological assays were carried out. The study was aimed at evaluating the; antimicrobial, anti-inflammatory activities, HIV-type 1 reverse transcriptase (RT) inhibition properties and to determine phenolic contents as well as evaluating the mutagenic properties of, 12 medicinal plants used by the Vha-Venda people against venereal and related diseases. An attempt was also made toward isolating and identification of the most active compounds from some extracts that were active against Neisseria gonorrhoeae. Twelve medicinal plants and various plant parts, Adansonia digitata (bark), Acacia karroo (bark), Aloe chabaudii (roots), Bolusanthus speciosus (leaves, bark and stem), Ekebergia capensis (leaves and bark), Elephantorrhiza burkei (roots), Grewia occidentalis (roots), Osyris lanceolata (roots), Pappea capensis (leaves), Peltophorum africanum (bark), Pterocarpus angolensis (leaves and bark) and Ximenia caffra (leaves and roots) were evaluated for their antimicrobial properties against two Gram-positive (Bacillus subtilis and Staphylococcus aureus), three Gram-negative (Neisseria gonorrhoeae, Escherichia coli and Klebsiella pneumonia) bacteria and the fungus Candida albicans. The plant materials were extracted with petroleum ether (PE), dichloromethane (DCM), 80% ethanol (EtOH) and water. Methanol was used for extracting materials for phenolic contents and HIV-1RT assays. The Disc diffusion method was used to determine gonococcal percentage inhibition and a microdilution assay was used to determine minimum inhibition concentration (MIC) and minimum fungicidal concentrations (MFC). Bolusanthus speciosus and X. caffra extracts exhibited the best antigonococcal, antifungal and antibacterial activities whilst A. digitata and A. chabaudii showed poor activities. The medicinal plants were also evaluated for cyclooxygenase (COX-1 and -2) and HIV-1 reverse transcriptase inhibition activity. The DCM and PE extracts of A. digitata bark, B. speciosus bark, P. angolensis bark and P. capensis leaves showed good anti-inflammatory activity against both COX-1 and COX-2. Methanol and water extracts of B. speciosus stems, P. africanum bark, P. angolensis leaves and P. capensis leaves exhibited good anti-HIV-1 RT activity. A. chabaudii roots, E. capensis bark and O. lanceolata roots showed low HIV-1 RT percentage inhibition. Phytochemical analysis using spectrophotometric methods revealed the presence of a variety of phenolic compounds in all the plant extracts including total phenolics, flavonoids, gallotannins and condensed tannins. High levels of total phenolics, flavonoids, gallotannins and condensed tannins were detected in X. caffra. Low amounts of flavonoids, gallotannins and condensed tannins were detected in B. speciosus. The Ames test using Salmonella typhimurium tester strain TA98 with and without S9 metabolic activation revealed that all plant extracts were non-mutagenic toward S. typhimurium strains TA98 without metabolic activation. However, E. burkei roots and E. capensis bark showed mutagenic effects toward TA98 after metabolic activation. Therefore, these two plants need to be used with caution, however more studies are required to confirm this result. Good antimicrobial activity observed in X. caffra leaves prompted an attempt to isolate active compounds. A pure compound from X. caffra leaves exhibited moderate activity (63%) against N. gonorrhoeae. However, the structure of the compound has as yet to be ratified. Pharmacological activity of the twelve medicinal plants used by Vha-Venda people against venereal and related diseases were validated in this study. The results obtained in this study give credence to the use of some of these plants. This study has further confirmed the need for screening these medicinal plants for more pharmacological activities. These plants may offer a new source of chemicals for the effective treatment of venereal and related diseases. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.