Potentiation of antimalarial activity of arteether in combination with Vetiver root extract

Abstract

<span style="font-size:11.0pt;mso-bidi-font-size: 10.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-bidi-font-family:"times="" roman";mso-ansi-language:en-gb;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="" lang="EN-GB">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 <i style="mso-bidi-font-style:normal">Vetiver zizanioides</i> (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 <i style="mso-bidi-font-style:normal">Plasmodium falciparum</i> (William H. Welch), respectively. Further, these combinations were explored against multidrug resistant rodent malaria parasite i.e. <i style="mso-bidi-font-style: normal">P</i>. <i style="mso-bidi-font-style:normal">yoelii</i> <i style="mso-bidi-font-style:normal">nigeriensis</i>. Analysis of <i style="mso-bidi-font-style:normal">in vivo</i> interaction of ART and VET showed that 10 mg/kg×5days of ART with 1000 mg/kg of VET ×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.</span>