Antiplasmodial triterpenoids from Ekebergia capensis.

From the stem bark of Ekebergia capensis, 10 new triterpenoid compounds, ekeberins A (1), B (2), C1 (3), C2 (4), C3 (5), D1 (6), D2 (7), D3 (8), D4 (9), and D5 (10), were isolated together with 17 known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the Mosher ester method. Several of these compounds were screened in vitro against both chloroquine (CQ)-sensitive and -resistant Plasmodium falciparum isolates and were found to exhibit moderate antiplasmodial activity, with compounds 20 (7-deacetoxy-7-oxogedunin) and 27 (2-hydroxymethyl-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene) showing IC50 values of 6 and 7 microM, respectively. Compound 27 at a dose of 500 mg/kg showed moderate parasitemia suppression of 52.9% against P. berghei NK 65 in a mouse model.

In Vivo antimalarial activity of aqueous extracts from Kenyan medicinal plants and their chloroquine (CQ) potentiation effects against a blood-induced CQ-resistant rodent parasite in mice.

Hot water extracts from eight medicinal plants representing five families, used for malaria treatment in Kenya were screened for their in vivo antimalarial activity in mice against a chloroquine (CQ) resistant Plasmodium berghei NK65, either alone or in combination with CQ. Extracts of three plants, Toddalia asiatica (root bark), Rhamnus prinoides (leaves and root bark) and Vernonia lasiopus (root bark) showed high chemosuppression in the range 51%-75%. Maytenus acuminata, M. heterophylla, M. senegalensis and Rhamnus staddo had moderate activities of 33%-49% parasitaemia suppression in the root bark and/or leaf extracts, while Withania somnifera (root bark) had a non-significant suppression (21%). In combination with CQ, extracts of V. lasiopus (all parts), leaf extracts of M. senegalensis, R. prinoides and T. asiatica as well as root barks of M. heterophylla, R. staddo and T. asiatica had improved parasitaemia suppression in the range 38%-66%, indicating synergistic interactions. Remarkable parasitaemia suppression by the extracts, either alone or in combination with CQ resulted into longer survival of mice relative to the controls, in some cases by more than 2 weeks. Plants, which showed significant antimalarial activity including V. lasiopus, T. asiatica and R. prinoides, should further be evaluated in the search for novel agents against drug-resistant malaria.

Antimalarial activity of methanolic extracts from plants used in Kenyan ethnomedicine and their interactions with chloroquine (CQ) against a CQ-tolerant rodent parasite, in mice.

Methanolic extracts from 15 medicinal plants representing 11 families, used traditionally for malaria treatment in Kenya were screened for their in vivo antimalarial activity in mice against a chloroquine (CQ)-tolerant Plasmodium berghei NK65, either alone or in combination with CQ. The plant parts used ranged from leaves (L), stem bark (SB), root bark (RB), seeds (S) and whole plant (W). When used alone, extracts from seven plants, Clerodendrum myricoides (RB), Ficus sur (L/SB/RB), Maytenus acuminata (L/RB), Rhamnus prinoides (L/RB), Rhamnus staddo (RB), Toddalia asiatica (RB) and Vernonia lasiopus (RB) had statistically significant parasitaemia suppressions of 31.7-59.3%. In combination with CQ, methanolic extracts of Albizia gummifera (SB), Ficus sur (RB), Rhamnus prinoides and Rhamnus staddo (L/RB), Caesalpinia volkensii (L), Maytenus senegalensis (L/RB), Withania somnifera (RB), Ekebergia capensis (L/SB), Toddalia asiatica (L/RB) and Vernonia lasiopus (L/SB/RB) gave statistically significant and improved suppressions which ranged from 45.5 to 85.1%. The fact that these activities were up to five-fold higher than that of extract alone may suggest synergistic interactions. Remarkable parasitaemia suppression by the extracts, either alone or in combination with CQ mostly resulted into longer mouse survival relative to the controls, in some cases by a further 2 weeks. Plants, which showed significant antimalarial activity including Vernonia lasiopus, Toddalia asiatica, Ficus sur, Rhamnus prinoides and Rhamnus staddo warrant further evaluation in the search for novel antimalarial agents against drug-resistant malaria.