Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei
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 com...
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ftdoajarticles:oai:doaj.org/article:cc525ad78b6249df87b7b694d9f92ff8 2023-05-15T15:14:48+02:00 Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei Elvis O. Ameyaw Kodwo B. Asmah Robert P. Biney Isaac T. Henneh Phyllis Owusu-Agyei James Prah Arnold D. Forkuo 2018-04-01T00:00:00Z https://doi.org/10.1186/s12936-018-2283-8 https://doaj.org/article/cc525ad78b6249df87b7b694d9f92ff8 EN eng BMC http://link.springer.com/article/10.1186/s12936-018-2283-8 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2283-8 1475-2875 https://doaj.org/article/cc525ad78b6249df87b7b694d9f92ff8 Malaria Journal, Vol 17, Iss 1, Pp 1-11 (2018) Malaria Artemisinin combination therapy Parasitemia Cryptolepine Xylopic acid Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2018 ftdoajarticles https://doi.org/10.1186/s12936-018-2283-8 2022-12-31T15:03:18Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 17 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Malaria Artemisinin combination therapy Parasitemia Cryptolepine Xylopic acid Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Artemisinin combination therapy Parasitemia Cryptolepine Xylopic acid Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Elvis O. Ameyaw Kodwo B. Asmah Robert P. Biney Isaac T. Henneh Phyllis Owusu-Agyei James Prah Arnold D. Forkuo Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei |
topic_facet |
Malaria Artemisinin combination therapy Parasitemia Cryptolepine Xylopic acid Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Elvis O. Ameyaw Kodwo B. Asmah Robert P. Biney Isaac T. Henneh Phyllis Owusu-Agyei James Prah Arnold D. Forkuo |
author_facet |
Elvis O. Ameyaw Kodwo B. Asmah Robert P. Biney Isaac T. Henneh Phyllis Owusu-Agyei James Prah Arnold D. Forkuo |
author_sort |
Elvis O. Ameyaw |
title |
Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei |
title_short |
Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei |
title_full |
Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei |
title_fullStr |
Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei |
title_full_unstemmed |
Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei |
title_sort |
isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in plasmodium berghei |
publisher |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12936-018-2283-8 https://doaj.org/article/cc525ad78b6249df87b7b694d9f92ff8 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 17, Iss 1, Pp 1-11 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12936-018-2283-8 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2283-8 1475-2875 https://doaj.org/article/cc525ad78b6249df87b7b694d9f92ff8 |
op_doi |
https://doi.org/10.1186/s12936-018-2283-8 |
container_title |
Malaria Journal |
container_volume |
17 |
container_issue |
1 |
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1766345203949502464 |