Phytochemical and antiplasmodial studies of five ethnobotanically-selected South African medicinal plants.

Doctoral Degree. University of KwaZulu-Natal, Pietermaritzburg.Vachellia xanthophloea, Euclea natalensis, Ozoroa obovata, Gardenia thunbergia, and Pappea capensis are traditionally used to treat malaria/fever in Africa. Previous studies showed that the extracts of V. xanthophloea, G. thunbergia, P. capensis, and E. natalensis have antiplasmodial activity. Therefore, in search of antiplasmodial compounds from South African plants, the five plants were investigated. Antiplasmodial screening of the ethyl acetate fraction of V. xanthophloea leaves against the 3D7 parasites showed moderate activity (IC50 = 10.6 μg/mL) and negligible cytotoxicity. Phytochemical investigation of the fraction afforded 16 compounds, ten flavonoids, a phenolic ester, a furofuran lignan, a carotenoid, and a fatty alcohol. The hexane fraction afforded a mixture of phytol and lupeol. Methyl gallate displayed the best antiplasmodial activity (IC50 = 1.2 μg/mL), better than the extract, and the cytotoxicity was not significant. The leaf extract of O. obovata inhibited P. falciparum viability by >90% at 50 μg/mL and was cytotoxic. Chromatographic purification of the extract afforded two biflavonoids, four flavonoid glycosides, a steroid glycoside, and a megastigmane derivative. The biflavonoids and flavonoid glycosides displayed nonselective antiplasmodial activities at 50 μg/mL. E. natalensis leaf extract displayed moderate antiplasmodial activity (IC50 = 25.6 μg/mL) and was not cytotoxic. Purification of the extract gave 11 compounds, six flavonoid glycosides, four triterpenoids, and a coumarin. The glycosides suppressed P. falciparum viability by more than 70% at 50 μg/mL but were also cytotoxic. An antiplasmodial assay of P. capensis leaf extract showed >80% inhibition of parasite viability at 50 μg/mL with cytotoxicity. Five flavonoid glycosides were subsequently isolated from the extract. The glycosides showed antiplasmodial activity at 50 μg/mL and were cytotoxic. G. thunbergia methanol leaf extract displayed good antiplasmodial activity (80% inhibition at 50 μg/mL) with little cytotoxicity. A saponin, two flavonoid glycosides, two metabolites of abscisic acid, a triterpenoid and a mixture of two sterols were isolated from the extract. The saponin and flavonoid glycosides inhibited the viability of P. falciparum at 50 μg/mL (>80%) but were also cytotoxic. This project has identified some extracts, e.g. V. xanthophloea and compounds, e.g. methyl gallate with promising antiplasmodial activity worthy of further development