NDLI: Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei

Content Provider	Springer Nature : BioMed Central
Author	Ameyaw, Elvis O. Asmah, Kodwo B. Biney, Robert P. Henneh, Isaac T. Owusu-Agyei, Phyllis Prah, James Forkuo, Arnold D.
Abstract	Background Increasing resistance to current anti-malarial therapies requires a renewed effort in searching for alternative therapies to combat this challenge, and combination therapy is the preferred approach to address this. The present study confirms the anti-plasmodial effects of two compounds, cryptolepine and xylopic acid and the relationship that exists in their combined administration determined. Methods Anti-plasmodial effect of cryptolepine (CYP) (3, 10, 30 mg kg−1) and xylopic acid (XA) (3, 10, 30 mg kg−1) was evaluated in Plasmodium berghei-infected male mice after a 6-day drug treatment. The respective doses which produced 50% chemosuppression (ED50) was determined by iterative fitting of the log-dose responses of both drugs. CYP and XA were then co-administered in a fixed dose combination of their ED50s (1:1) as well as different fractions of these combinations (1/2, 1/4, 1/8, 1/16 and 1/32) to find the experimental ED50 (Zexp). The nature of interaction between cryptolepine and xylopic acid was determined by constructing an isobologram to compare the Zexp with the theoretical ED50 (Zadd). Additionally, the effect of cryptolepine/xylopic acid co-administration on vital organs associated with malarial parasiticidal action was assessed. Results The Zadd and Zexp were determined to be 12.75 ± 0.33 and 2.60 ± 0.41, respectively, with an interaction index of 0.2041. The Zexp was significantly (P < 0.001) below the additive isobole indicating that co-administration of cryptolepine and xylopic acid yielded a synergistic anti-plasmodial effect. This observed synergistic antiplasmodial effect did not have any significant deleterious effect on the kidney, liver and spleen. However, the testis were affected at high doses. Conclusion The co-administration of cryptolepine and xylopic acid produces synergistic anti-malarial effect with minimal toxicity.
Related Links	https://malariajournal.biomedcentral.com/counter/pdf/10.1186/s12936-018-2283-8.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
ISSN	14752875
DOI	10.1186/s12936-018-2283-8
Journal	Malaria Journal
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2018-04-04
Access Restriction	Open
Subject Keyword	Parasitology Tropical Medicine Infectious Diseases Entomology Microbiology Public Health Malaria Artemisinin combination therapy Parasitemia Cryptolepine Xylopic acid
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology
Journal Impact Factor	2.4/2023
5-Year Journal Impact Factor	2.6/2023

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