In vitro and in vivo evaluation of Noscapine as a potential antimalarial vis-à-vis standard Dihydroartemisinin (DHA) against Plasmodium falciparum 3D7, P. falciparum clinical isolate Pf140/SS and P. berghei ANKA

Abstract

Malaria is a global public health menace. The quest for new antimalarials and adjuvants for malaria in the backdrop of artemisinin resistance has been enormous. This study evaluates the comprehensive antimalarial activity of the natural phytochemical compound Noscapine, against Plasmodium falciparum 3D7 strain (Pf3D7), clinical isolate (Pf140/SS) and in Plasmodium berghei ANKA (PbA), inhibiting in vitro and in vivo parasite growth under controlled conditions as evaluated through the ring-stage survival assay, phenotypic assessments and SYBR-green based fluorescence assay. Cytotoxicity of Noscapine was evaluated against the J774. A.1 murine macrophage cell line besides profiling its hemolysis activities against human RBCs. The antimalarial efficacy of Noscapine against Pf3D7 and Pf140/SS was similar or better than standard antimalarial Dihydroartemisinin (DHA), with the IC50 value of 7.68±0.88 and 5.57±0.74 nM/mL respectively along with more than 95% inhibition in infected Wister albino rats with PbA after 4-day suppressive test. Importantly, unlike DHA, no toxicity symptoms were observed with CC50 value 1748 nM/mL or hemolysis with Nospcapine, even at extremely high concentrations. Based on the published literature as on date, this is the first report on native Noscapine, which has shown potent antimalarial efficacy and safety profiles vis-à-vis standard antimalarial DHA, demonstrated through in vitro and in vivo models of animal and clinical malaria parasites.