目的:青蒿素联合治疗,尼日利亚的一线抗疟药,据报道,在疟疾治疗方面遭受了多次失败,因此寻找其他化合物的新组合。据报道,没食子酸甲酯和巴马汀具有抗疟原虫活性,但尚未评估其组合的抗疟疾活性。因此,在胡椒碱存在下,对没食子酸甲酯和巴马汀的组合在体外和体内的抗疟疾活性进行了评估。
方法:体外研究了没食子酸甲酯和巴马汀组合对β-血色素形成的抑制潜力。此外,在感染伯氏疟原虫NK65的小鼠中评估了没食子酸甲酯和巴马汀联合使用或不使用生物增强剂(胡椒碱)的抗疟活性。
结果:没食子酸甲酯和巴马汀以3:2的比例在体外协同作用,对β-血色素(嗜血色素)形成具有最高的抑制作用(IC50=0.73µg/mL)。没食子酸甲酯和巴马汀的3:2组合在不存在胡椒碱的情况下在体内不表现出抗疟疾活性,但在小鼠接种后第6天和第8天,在25mg/kg体重的胡椒碱存在下,导致寄生虫血症减少超过40%。
结论:在胡椒碱存在下,没食子酸甲酯和巴马汀的3:2组合在体内表现出抗疟活性,可能是通过协同抑制疟原虫食物液泡中血红素的形成而导致的。和它的死亡。
OBJECTIVE: Artemisinin combination therapies, the first-line antimalarials in Nigeria, have reportedly suffered multiple failures in malaria treatment, hence the search for novel combination of other compounds. Methyl gallate and palmatine have been reported to exhibit antiplasmodial activities but the antimalarial activity of their combination has not been evaluated. Therefore, the evaluation of the combination of methyl gallate and palmatine for antimalarial activity in vitro and in vivo in the presence of piperine was carried out.
METHODS: The inhibitory potential of methyl gallate and palmatine combination on β-hematin (hemozoin) formation was studied in vitro. Also, the antimalarial activity of methyl gallate and palmatine combination with/without a bioenhancer (piperine) was evaluated in Plasmodium berghei NK65-infected mice.
RESULTS: Methyl gallate and palmatine in the ratio 3:2 acted synergistically in vitro and had the highest inhibitory effect (IC50 = 0.73 µg/mL) on β-hematin (hemozoin) formation. The 3:2 combination of methyl gallate and palmatine exhibited no antimalarial activity in vivo in the absence of piperine but caused reduction in parasitemia that exceeded 40% in the presence of piperine at the dose of 25 mg/kg body weight on days 6 and 8 post-inoculation in mice.
CONCLUSIONS: The 3:2 combination of methyl gallate and palmatine in the presence of piperine exhibited antimalarial activity in vivo, possibly by synergistic inhibition of hemozoin formation which may cause accumulation of haem within the food vacuole of Plasmodium spp. and its death.