Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice

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. Antiplasmodial effect of xylopic acid (XA: 3, 10, 30, 100, 150 mg kg ), artesunate (ART: 1, 2, 4, 8, 16 mg kg ), and amodiaquine (AQ: 1.25, 2.5, 5, 10, 20 mg kg ) were evaluated in Plasmodium berghei (strain ANKA)-infected mice to determine respective ED s. Artemether/lumefantrine was used as the positive control. XA/ART and XA/AQ were subsequently administered in a fixed-dose combination of their ED s (1:1) and the combination fractions of their ED s (1/2, 1/4, 1/8, 1/16, and 1/32) to determine the experimental ED s (Z ). An isobologram was constructed to determine the nature of the interaction between XA/ART, and XA/AQ combinations by comparing Z with the theoretical ED (Z ). Bodyweight and 30-day survival post-treatment were additionally recorded. ED s for XA, ART, and AQ were 9.0 ± 3.2, 1.61 ± 0.6, and 3.1 ± 0.8 mg kg , respectively. The Z , Z 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 Z for both combination therapies lay significantly (p