Research On The Efficacy Of Polyalthia Longifolia Var.pendula Leaf Ethanol Extract Treating Plasmodium Berghei Sensitive Malaria Mice And Artemisinin Resistant Malaria Mice

Objective:Malaria is one of the insect-borne infectious diseases that seriously endanger human health.Across many countries and regions,there have been clinical reports of decreased susceptibility to traditional antimalarial drugs.Therefore,it is necessary to screen out novel potential antimalarial drugs.As a traditional tropical plant,Polyalthia longifolia var.pendula has been reported to have good antimalarial properties and low toxicity in its leaf extract,and could be used as a good source of new antimalarial drugs.Under this background,a highly resistant and stably inherited model of Artemisinin-resistant Plasmodium berghei was developed on the basis of the existing models.The acute toxicity of the ethanol leaf extract of P.longifolia and its rational dosage were investigated through experiments.Different doses of the extract were used to test the efficacy on treating Artemisinin-resistant and sensitive P.berghei infected mice.The antimalarial characteristics of P.longifolia were verified by the analysis of the experimental results.Methods:1.According to the principle of gradually increasing administration in resistance cultivation,artemisinin-resistant strains of P.berghei were continued to be cultivated until the 53rd generation.Its ED₅₀0 and resistance index were obtained.2.Acute toxicity test was carried out by maximum dose method after ethanol extraction.The weight,mortality and pathological changes of organs in mice were compared,and a reasonable dosage range was obtained.3.In the experiment,artemisinin-resistant and susceptible mice of P.berghei were used as models.After 48 hours of administration and once a week,tail blood smears were taken for microscopic examination.The average infection rate,inhibition rate,negative conversion rate and 14-day curative rate of P.berghei were calculated.Then the body weight,coefficients of liver and spleen,pathological changes of liver and spleen and liver function in serum of mice were correlated.The changes in total bilirubin?TBil?,alanine aminotransferase?ALT?,aspartate aminotransferase?AST?were analyzed.The efficacy of different doses of ethanol extract of P.longifolia and standard doses of artemisinin on P.berghei artemisinin-resistant and susceptible mice were compared.Results:1.The Plasmodium berghei artemisinin-resistant mouse malaria model was cultured to 53 generations with an ED₅₀0 of 4165.31 mg/kg and a resistance index of16.50,which was higher than the previous experiments and related literature resistance index.2.After intragastric administration of the extract at the maximum concentration,5000mg/kg,there were no significant abnormalities in general condition,motality,body weight,spleen and liver organ coefficients,and pathological observation of organs among blank groups?P<0.05?.3.Among P.berghei sensitive mice groups,the 14-day curative rate of artemisinin group at standard dose was the highest?90%?.Compared with the blank group,there was no significant difference in parasite infection index,spleen coefficient and serum liver biochemical index?P<0.05?.The ethanol extract at 2times standard dose was still higher than other groups with low doses,and the 14-day curative rate was 50%.4.In the malaria of Plasmodium berghei artemisinin-resistant mice groups,the therapeutic effect of the ethanol leaf extract of P.longifolia?1600 mg/kg?at the standard of 2 times was most pronounced.The average infection rate of resistant mice given 2 times the standard dose of P.longifolia leaf extract was 1.83±1.03%,which was significantly lower than that of the other groups?P<0.05?.The average inhibition rate was 88.13±0.75%,and the inhibitory effect was the most obvious?P<0.05?.At the same time,40%of the infected mice showed different degrees of negative conversion,and the complete cure rate of the mice was 30%after 14 days of administration,which was also higher than that of the other groups of mice including the artemisinin group.The liver and spleen coefficient such as TBIL,ALT and AST were lower than the other groups,which were close to the normal value?P<0.05?.Conclusion:1.The mouse model of artemisinin-resistant P.berghei was established,with high resistance index and stable cultivation.2.LD₅₀0 of the ethanol extract of P.longifolia is far greater than 5000mg/kg,which is safe and non-toxic at this concentration.3.2 times standard dose?1600mg/kg?has obvious curative effect on artemisinin resistant and sensitive P.berghei.It can kill Plasmodium berghei to varying degrees,especially in artemisinin-resistant malaria,and has good prospects for antimalarial drug development.