Claire Beaufay1, Marie-France Hérent2, Joëlle Quetin-Leclercq2, Joanne Bero2. 1. Pharmacognosy Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue E. Mounier 72, B1.72.03, 1200, Brussels, Belgium. Claire.beaufay@uclouvain.be. 2. Pharmacognosy Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue E. Mounier 72, B1.72.03, 1200, Brussels, Belgium.
Abstract
BACKGROUND: Considering the need for new anti-malarial drugs, further investigations on Keetia leucantha (Rubiaceae), an in vitro antiplasmodial plant traditionally used to treat malaria, were carried out. This paper aimed to assess the in vivo anti-malarial efficacy of K. leucantha triterpenic esters previously identified as the most in vitro active components against Plasmodium falciparum and their potential toxicity as well as those of anti-malarial extracts. RESULTS: These eight triterpenic esters and the major antiplasmodial triterpenic acids, ursolic and oleanolic acids, were quantified in the twigs dichloromethane extract by validated HPLC-UV methods. They account for about 19% of this extract (16.9% for acids and 1.8% for esters). These compounds were also identified in trace in the twigs decoction by HPLC-HRMS. Results also showed that extracts and esters did not produce any haemolysis, and were devoid of any acute toxicity at a total cumulative dose of 800 and 150 mg/kg respectively. Moreover, esters given intraperitoneally at 50 mg/kg/day to Plasmodium berghei-infected mice showed a very significant (p < 0.01) parasitaemia inhibition (27.8 ± 5.4%) on day 4 post-infection compared to vehicle-treated mice. CONCLUSIONS: These results bring out new information on the safety of K. leucantha use and on the identification of anti-malarial compounds from its dichloromethane extract. Its activity can be explained by the presence of triterpenic acids and esters which in vivo activity and safety were demonstrated for the first time.
BACKGROUND: Considering the need for new anti-malarial drugs, further investigations on Keetia leucantha (Rubiaceae), an in vitro antiplasmodial plant traditionally used to treat malaria, were carried out. This paper aimed to assess the in vivo anti-malarial efficacy of K. leucantha triterpenic esters previously identified as the most in vitro active components against Plasmodium falciparum and their potential toxicityas well as those of anti-malarial extracts. RESULTS: These eight triterpenic esters and the major antiplasmodial triterpenic acids, ursolic and oleanolic acids, were quantified in the twigs dichloromethane extract by validated HPLC-UV methods. They account for about 19% of this extract (16.9% for acids and 1.8% for esters). These compounds were also identified in trace in the twigs decoction by HPLC-HRMS. Results also showed that extracts and esters did not produce any haemolysis, and were devoid of any acute toxicity at a total cumulative dose of 800 and 150 mg/kg respectively. Moreover, esters given intraperitoneally at 50 mg/kg/day to Plasmodium berghei-infected mice showed a very significant (p < 0.01) parasitaemia inhibition (27.8 ± 5.4%) on day 4 post-infection compared to vehicle-treated mice. CONCLUSIONS: These results bring out new information on the safety of K. leucantha use and on the identification of anti-malarial compounds from its dichloromethane extract. Its activity can be explained by the presence of triterpenic acids and esters which in vivo activity and safety were demonstrated for the first time.
Authors: Petr Dzubak; Marian Hajduch; David Vydra; Alica Hustova; Miroslav Kvasnica; David Biedermann; Lenka Markova; Milan Urban; Jan Sarek Journal: Nat Prod Rep Date: 2006-05-03 Impact factor: 13.423
Authors: Matheus Santos de Sá; José Fernando Oliveira Costa; Antoniana Ursine Krettli; Mariano Gustavo Zalis; Gabriela Lemos de Azevedo Maia; Ivana Maria Fechine Sette; Celso de Amorim Câmara; José Maria Barbosa Filho; Ana Maria Giulietti-Harley; Ricardo Ribeiro Dos Santos; Milena Botelho Pereira Soares Journal: Parasitol Res Date: 2009-04-15 Impact factor: 2.289