Dhawan Sangeeta, Gunjan Sarika, Pal Anirban, Tripathi Renu
Indian J Exp Biol. 2016 May;54(5):315-21.
In malaria, development of resistance towards artemisinin derivatives has urged the need for new drugs or new drug combinations to tackle the drug resistant malaria. We studied the fresh root extract of Vetiver zizanioides (Linn.) Nash (VET) with a CDRI-CIMAP antimalarial α/β arteether (ART) together for their antimalarial potential. Our results showed additive to synergistic antimalarial activity of VET and ART with sum fractional inhibitory concentrations Σ FICs 1.02 ± 0.24 and 1.12 ± 0.32 for chloroquine sensitive (CQS) and chloroquine resistant (CQR) strain of Plasmodium falciparum (William H. Welch), respectively. Further, these combinations were explored against multidrug resistant rodent malaria parasite i.e. P. yoelii nigeriensis. Analysis of in vivo interaction of ART and VET showed that 10 mg/kg x 5 days of ART with 1000 mg/kg of VET x 5 days cured 100% mice infected with MDR parasite, while the same dose of ART could produce only up to 30% cure and VET fraction was not curative at all. Synergism/additiveness, found between VET and ART is reported for the first time. The curative dose of ART in the combination was reduced to its one fourth, and thus limits the side effects, if any. Although antimalarial potential of ART was enhanced by VET, action mechanism of later needs to be elucidated in detail.
在疟疾中，对青蒿素衍生物产生耐药性促使人们需要新的药物或新的药物组合来应对耐药性疟疾。我们研究了香根草（Vetiver zizanioides (Linn.) Nash，VET）的新鲜根提取物与一种由中央药物研究所（CDRI）-中央药物与植物化学研究所（CIMAP）研制的抗疟药α/β蒿甲醚（ART）联合使用时的抗疟潜力。我们的结果显示，VET和ART对恶性疟原虫（William H. Welch）氯喹敏感（CQS）株和氯喹耐药（CQR）株具有相加至协同的抗疟活性，其联合分数抑制浓度总和（ΣFICs）分别为1.02±0.24和1.12±0.32。此外，还对这些组合针对多药耐药的啮齿动物疟原虫即约氏疟原虫尼氏亚种进行了研究。对ART和VET体内相互作用的分析表明，10mg/kg×5天的ART与1000mg/kg×5天的VET可使100%感染多药耐药寄生虫的小鼠治愈，而相同剂量的ART仅能达到30%的治愈率，单独使用VET则完全没有治愈效果。VET和ART之间的协同/相加作用是首次报道。联合用药中ART的治愈剂量降至其四分之一，因此如果有副作用的话，也将副作用限制到了最低。尽管VET增强了ART的抗疟潜力，但其作用机制仍需详细阐明。
