Synergistic anti-malarial action of cryptolepine and artemisinins

Malaria Journal

Research

Johnson N. Boampong¹  Elvis O. Ameyaw¹  Ben A. Gyan²  Michael F. Ofori²  Andrea T. Arku²  Kwesi M. Boadu³  Charles Ansah³  Arnold D. Forkuo³ 

[1] Department of Biomedical and Forensic Sciences, School of Biological Science, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana;Department of Immunology, Noguchi Memorial Institute for Biomedical Research, University of Ghana, Legon, Ghana;Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;

关键词: Cryptolepis sanguinolenta;    Cryptolepine;    Malaria;    Anti-malarial drug combinations;    Artemisinins;    Synergy;   

DOI  :  10.1186/s12936-016-1137-5

 received in 2015-12-02, accepted in 2016-01-29,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives.MethodsThe in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane’s test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd.ResultsCPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Zadd of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg−1po) and in combination with ART (4 mg kg−1) showed no significant difference compared to the control group.ConclusionThe combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.

【 授权许可】

CC BY   
© Forkuo et al. 2016