Noscapine shows antimalarial activity against Plasmodium falciparum 3D7, its clinical isolate Pf140/SS, and Plasmodium berghei ANKA

Abstract

Objective: To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain (Pf3D7), its clinical isolate (Pf140/SS), and Plasmodium berghei ANKA (PbA). Methods: Using ring-stage survival assay, phenotypic assessments, and SYBR-green-based fluorescence assay, the antimalarial activities of noscapine were assessed compared with dihydroartemisinin (DHA) in in vivo and in vitro studies. In addition, hemolysis and cytotoxicity tests were carried out to evaluate its safety. RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2 (PfFP-2). Results: The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA, with IC₅₀ values of (7.68±0.88) and (5.57±0.74) nM/mL, respectively, and >95% inhibition of PbA infected rats. Noscapine also showed a safe profile, as evidenced by low hemolysis and cytotoxicity even at high concentrations. Moreover, PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS (P<0.01). Conclusions: Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles, which may be further explored as a therapeutic candidate for the treatment of malaria.

Keywords

Malaria / Plasmodium falciparum / Plasmodium berghei / Noscapine / Antimalarial / Dihydroartemisinin / Cytotoxicity / Falcipain-2

Acknowledgments

The authors express their indebtedness to the Director, Ispat General Hospital and to the Chairman, Community Welfare Society Hospital and CSCMi (NIH-ICEMR-India) for providing laboratory facilities and necessary technical support to enable the malaria experiments to be conducted successfully. Authors acknowledge OHEPEE Government of Odisha, for the support under Centre of Excellence for Natural products and therapeutics at the Department of Biotechnology and Bioinformatics, Sambalpur University, Burla, Odisha for providing the laboratory facilities to conduct the experiments. SKB acknowledges the award of research fellowship (DST/INSPIRE/IF180684) by the Department of Science and Technology, Government of India. Authors also gratefully acknowledge the generous help from BEI Resources, NIAID, and NIH, USA for providing the following biological reagents: Plasmodium falciparum strain 3D7, MRA-102, contributed by Daniel J. Carucci and Plasmodium berghei strain ANKA, MRA-671, contributed by Mark F. Wiser.

Conflict of interest statement

The authors declare no conflict of interest.

Funding

The study received no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

PKS and PKN conceptualized the study. SKB performed the experiments and investigation with inputs and support from S. Maharana, SC, and DRS. AN, SK, S. Mohanty, PKB, PKN, and PKS monitored and supervised the experiments on-site. PKN, PKS, AN, and SK provided the resources. SKB and PKS did the formal analysis. PKS and PKN supervised the study. SKB wrote the manuscript. PKS edited the manuscript.

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