Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice.
Malar J
; 20(1): 113, 2021 Feb 25.
Article
en En
| MEDLINE
| ID: mdl-33632233
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 (11) 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 co-administration with either artesunate or amodiaquine produces a synergistic anti-plasmodial effect in mice infected with P. berghei.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diterpenos de Tipo Kaurano
/
Artesunato
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Amodiaquina
/
Malaria
/
Antimaláricos
Límite:
Animals
Idioma:
En
Revista:
Malar J
Asunto de la revista:
MEDICINA TROPICAL
Año:
2021
Tipo del documento:
Article
País de afiliación:
Ghana