ABSTRACT
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.
Subject(s)
Administration, Oral , Ajuga/metabolism , Animals , Antimalarials/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Malaria/therapy , Mice , Mice, Inbred BALB C , Phytotherapy/methods , Plant Extracts/pharmacology , Plant Leaves/metabolism , Plasmodium berghei/metabolism , Time FactorsABSTRACT
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.
Subject(s)
Animals , Mice , Chloroquine/pharmacology , Erythrocytes/drug effects , Oxidative Stress/drug effects , Plasmodium berghei/drug effects , Quinolines/pharmacology , Erythrocytes/parasitology , Lipid Peroxidation , Mice, Inbred BALB C , Plasmodium berghei/metabolism , Superoxide Dismutase/metabolismABSTRACT
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