Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice
Abstract Background Evidence of Plasmodium resistance to some of the current anti-malarial agents makes it imperative to search for newer and effective drugs to combat malaria. Therefore, this study evaluated whether the co-administrations of xylopic acid-amodiaquine and xylopic acid-artesunate comb...
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ftdoajarticles:oai:doaj.org/article:bd829dff2fbb4027b2d1abea076a47c9 2023-05-15T15:18:18+02:00 Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice Silas Acheampong Osei Robert Peter Biney Ernest Obese Mary Atta-Panyi Agbenyeku Isaac Yaw Attah Elvis Ofori Ameyaw Johnson Nyarko Boampong 2021-02-01T00:00:00Z https://doi.org/10.1186/s12936-021-03658-6 https://doaj.org/article/bd829dff2fbb4027b2d1abea076a47c9 EN eng BMC https://doi.org/10.1186/s12936-021-03658-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03658-6 1475-2875 https://doaj.org/article/bd829dff2fbb4027b2d1abea076a47c9 Malaria Journal, Vol 20, Iss 1, Pp 1-13 (2021) Antimalarial drugs Combination therapies Isobolographic analysis Xylopic acid Artesunate Amodiaquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2021 ftdoajarticles https://doi.org/10.1186/s12936-021-03658-6 2022-12-31T09:40:14Z Abstract Background Evidence of Plasmodium resistance to some of the current anti-malarial agents makes it imperative to search for newer and effective drugs to combat malaria. Therefore, this study evaluated whether the co-administrations of xylopic acid-amodiaquine and xylopic acid-artesunate combinations will produce a synergistic anti-malarial effect. Methods Antiplasmodial effect of xylopic acid (XA: 3, 10, 30, 100, 150 mg kg−1), artesunate (ART: 1, 2, 4, 8, 16 mg kg−1), and amodiaquine (AQ: 1.25, 2.5, 5, 10, 20 mg kg−1) were evaluated in Plasmodium berghei (strain ANKA)-infected mice to determine respective ED50s. Artemether/lumefantrine was used as the positive control. XA/ART and XA/AQ were subsequently administered in a fixed-dose combination of their ED50s (1:1) and the combination fractions of their ED50s (1/2, 1/4, 1/8, 1/16, and 1/32) to determine the experimental ED50s (Zexp). An isobologram was constructed to determine the nature of the interaction between XA/ART, and XA/AQ combinations by comparing Zexp with the theoretical ED50 (Zadd). Bodyweight and 30-day survival post-treatment were additionally recorded. Results ED50s for XA, ART, and AQ were 9.0 ± 3.2, 1.61 ± 0.6, and 3.1 ± 0.8 mg kg−1, respectively. The Zadd, Zexp, and interaction index for XA/ART co-administration was 5.3 ± 2.61, 1.98 ± 0.25, and 0.37, respectively while that of XA/AQ were 6.05 ± 2.0, 1.69 ± 0.42, and 0.28, respectively. The Zexp for both combination therapies lay significantly (p < 0.001) below the additive isoboles showing XA acts synergistically with both ART and AQ in clearing the parasites. High doses of XA/ART combination significantly (p < 0.05) increased the survival days of infected mice with a mean hazard ratio of 0.40 while all the XA/AQ combination doses showed a significant (p < 0.05) increase in the survival days of infected mice with a mean hazard ratio of 0.27 similar to AL. Both XA/ART and XA/AQ combined treatments significantly (p < 0.05) reduced weight loss. Conclusion Xylopic acid ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 20 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Antimalarial drugs Combination therapies Isobolographic analysis Xylopic acid Artesunate Amodiaquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Antimalarial drugs Combination therapies Isobolographic analysis Xylopic acid Artesunate Amodiaquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Silas Acheampong Osei Robert Peter Biney Ernest Obese Mary Atta-Panyi Agbenyeku Isaac Yaw Attah Elvis Ofori Ameyaw Johnson Nyarko Boampong Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice |
topic_facet |
Antimalarial drugs Combination therapies Isobolographic analysis Xylopic acid Artesunate Amodiaquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Evidence of Plasmodium resistance to some of the current anti-malarial agents makes it imperative to search for newer and effective drugs to combat malaria. Therefore, this study evaluated whether the co-administrations of xylopic acid-amodiaquine and xylopic acid-artesunate combinations will produce a synergistic anti-malarial effect. Methods Antiplasmodial effect of xylopic acid (XA: 3, 10, 30, 100, 150 mg kg−1), artesunate (ART: 1, 2, 4, 8, 16 mg kg−1), and amodiaquine (AQ: 1.25, 2.5, 5, 10, 20 mg kg−1) were evaluated in Plasmodium berghei (strain ANKA)-infected mice to determine respective ED50s. Artemether/lumefantrine was used as the positive control. XA/ART and XA/AQ were subsequently administered in a fixed-dose combination of their ED50s (1:1) and the combination fractions of their ED50s (1/2, 1/4, 1/8, 1/16, and 1/32) to determine the experimental ED50s (Zexp). An isobologram was constructed to determine the nature of the interaction between XA/ART, and XA/AQ combinations by comparing Zexp with the theoretical ED50 (Zadd). Bodyweight and 30-day survival post-treatment were additionally recorded. Results ED50s for XA, ART, and AQ were 9.0 ± 3.2, 1.61 ± 0.6, and 3.1 ± 0.8 mg kg−1, respectively. The Zadd, Zexp, and interaction index for XA/ART co-administration was 5.3 ± 2.61, 1.98 ± 0.25, and 0.37, respectively while that of XA/AQ were 6.05 ± 2.0, 1.69 ± 0.42, and 0.28, respectively. The Zexp for both combination therapies lay significantly (p < 0.001) below the additive isoboles showing XA acts synergistically with both ART and AQ in clearing the parasites. High doses of XA/ART combination significantly (p < 0.05) increased the survival days of infected mice with a mean hazard ratio of 0.40 while all the XA/AQ combination doses showed a significant (p < 0.05) increase in the survival days of infected mice with a mean hazard ratio of 0.27 similar to AL. Both XA/ART and XA/AQ combined treatments significantly (p < 0.05) reduced weight loss. Conclusion Xylopic acid ... |
format |
Article in Journal/Newspaper |
author |
Silas Acheampong Osei Robert Peter Biney Ernest Obese Mary Atta-Panyi Agbenyeku Isaac Yaw Attah Elvis Ofori Ameyaw Johnson Nyarko Boampong |
author_facet |
Silas Acheampong Osei Robert Peter Biney Ernest Obese Mary Atta-Panyi Agbenyeku Isaac Yaw Attah Elvis Ofori Ameyaw Johnson Nyarko Boampong |
author_sort |
Silas Acheampong Osei |
title |
Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice |
title_short |
Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice |
title_full |
Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice |
title_fullStr |
Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice |
title_full_unstemmed |
Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice |
title_sort |
xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in plasmodium berghei-infected mice |
publisher |
BMC |
publishDate |
2021 |
url |
https://doi.org/10.1186/s12936-021-03658-6 https://doaj.org/article/bd829dff2fbb4027b2d1abea076a47c9 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 20, Iss 1, Pp 1-13 (2021) |
op_relation |
https://doi.org/10.1186/s12936-021-03658-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03658-6 1475-2875 https://doaj.org/article/bd829dff2fbb4027b2d1abea076a47c9 |
op_doi |
https://doi.org/10.1186/s12936-021-03658-6 |
container_title |
Malaria Journal |
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20 |
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1 |
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1766348504754552832 |