Antiplasmodial activity of Ajuga bracteosa against Plasmodium berghei infected BALB/c mice.

Background & objectives: The present work was undertaken to evaluate antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant Ajuga bracteosa in Plasmodium berghei infected BALB/c mice along with its phytochemical screening and acute toxicity test to support its traditional use as a remedy for malaria. Methods: Plant extract (ethanolic) 250, 500, 750 mg/kg/day was evaluated in the early and established infection along with repository activity in P. berghei infected BALB/c mice through suppressive, curative and preventive test. The phytochemical screening was carried out by employing standard procedures. The acute toxicity was checked through limit test. Results: The ethanolic leaves extract of A. bracteosa (250, 500 and 750 mg/kg/day) demonstrated a dose-dependent chemosuppression during early and in established infections, along with significant (P<0.05) repository activity. At a concentration of 750 mg/kg/day maximum 77.7 per cent chemosuppression during early infection and 68.8 per cent chemosuppression in repository activity were found. This dose enhanced significant mean survival period up to 27.4 ± 0.46 days in established infection. ELEAB was found to be safe up to 5 g/kg weight when administrated orally in the female BALB/c mice, which is upper limit for oral administration of the test material to rodents. ED50 of ELEAB was 300 mg/kg body weight of mice. Interpretation & conclusion: ELEAB inhibited parasitaemia and enhanced mean survival time in a dose-dependent manner upto 750 mg/kg/day dose in treated mice. Further studies need to be done to isolate and characterize active constituents of extract and to study their mechanism of action.

Modification of oxidative status in Plasmodium berghei-infected erythrocytes by E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline compared to chloroquine

E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline (IQ) is a new quinoline derivative which has been reported as a haemoglobin degradation and ß-haematin formation inhibitor. The haemoglobin proteolysis induced by Plasmodium parasites represents a source of amino acids and haeme, leading to oxidative stress in infected cells. In this paper, we evaluated oxidative status in Plasmodium berghei-infected erythrocytes in the presence of IQ using chloroquine (CQ) as a control. After haemolysis, superoxide dismutase (SOD), catalase, glutathione cycle and NADPH + H+-dependent dehydrogenase enzyme activities were investigated. Lipid peroxidation was also assayed to evaluate lipid damage. The results showed that the overall activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were significantly diminished by IQ (by 53.5 percent and 100 percent, respectively). Glutathione peroxidase activity was also lowered (31 percent) in conjunction with a higher GSSG/GSH ratio. As a compensatory response, overall SOD activity increased and lipid peroxidation decreased, protecting the cells from the haemolysis caused by the infection. CQ shared most of the effects showed by IQ; however it was able to inhibit the activity of isocitrate dehydrogenase and glutathione-S-transferase. In conclusion, IQ could be a candidate for further studies in malaria research interfering with the oxidative status in Plasmodium berghei infection.

Estudo sobre a possível atividade terapêutica da deferoxamina na infecçäo experimental de camundongos pelo Plasmodium berghei / The possible therapeutic activity of deferoxamine in experimental infections of mice by Plasmodium berghei

A deferoxamina é substância química dotada de propriedades quelantes relativas aos sais de ferro. A depleçäo desse mineral no organismo poderia influir, segundo algumas opiniöes, sobre o metabolismo de plasmódios que se desenvolvem no interior das hemácias. Para analisar essa possibilidade administramos doses cotidianas de 300 ou 1.000 mg/Kg do composto, durante cinco e 15 dias, a camundongos infectados pelo Plasmodium berghei. A mortalidade dos animais e a contagem do número de parasitas no sangue foram os parâmetros utilizados para verificar a atividade da deferoxamina. Os resultados evidenciaram aumento gradual e progressivo da mortalidade e da parasitemia em todos os roedores, sem diferenças constatadas nos controles. Assim, pelo menos de acordo com o estudo efetuado, dependente de modelo experimental, a substância näo se mostrou promissora para o tratamento da malária