Voacanga africana-artesunate and Voacanga africana-amodiaquine combinations as effective anti-plasmodial agents in mice

Abstract

Background

Malaria is a global health problem due to its high incidence of morbidity and mortality, especially in children and pregnant women. However, the Plasmodium parasite frequently develops resistance to chemotherapy, triggering continuous research for effective treatment options for malaria. Therefore, this study investigated the potential anti-plasmodial effect of Voacanga africana (VA)-artesunate and VA-amodiaquine combinations in mice.

Methods

We collected VA seeds from Kumasi, Ghana, and macerated them with petroleum ether to obtain a yield of 4.2%. Acute toxicity testing of VA was carried out with doses of 0 – 3000 mg/kg. The anti-plasmodial effects of VA at doses 0 – 300 mg/kg were assessed in Plasmodium berghei (strain ANKA)-infected mice using 4-day suppressive and Rane's curative tests. A combination of various fractions (1, 1/2, 1/4 and 1/16) of VA-artesunate or VA-amodiaquine was used to determine their experimental ED₅₀ s (Z_exp). We used an isobologram to determine the combination index (CI) and the nature of the interaction between VA-artesunate or VA-amodiaquine combinations by comparing the CI with Z_exp. The anti-plasmodial effects of VA alone or in combination with artesunate or amodiaquine were compared by ANOVA, and p < 0.05 was considered statistically significant.

Results

VA at doses 0 – 300 mg/kg showed no toxicity in the mice, whereas VA at a dose of 3000 mg/kg resulted in the death of mice after 24 h. The LD₅₀ was estimated to be 1763 mg/kg. Treatment of mice with VA alone at doses (30, 100 and 300 mg/kg) significantly (p < 0.05) reduced parasitaemia levels in mice when compared to the normal saline control group. Similarly, artesunate and VA (30, 100 and 300 mg/kg) showed a significant (p < 0.01) reduction in body temperature as compared to the control. ED₅₀ s for VA, artesunate, and amodiaquine were 202 ± 0.22 mg/kg, 5.4 ± 0.24 mg/kg, and 16.83 ± 0.28 mg/kg, respectively. CI for VA-artesunate and VA-amodiaquine were 0.002 and 37,094.1 respectively. The CI for VA-artesunate was significantly (p = 0.0001) below the additive isobole (CI<1) showing a synergistic effect of this combination in reducing parasite levels and increasing the mean survival of mice.

Conclusions

VA showed a moderate antimalarial activity when used in monotherapy, while a combination of VA and AT showed synergism against P. beighei infection by reducing parasitemia levels, preventing hemolysis, decreasing PCV, increasing body temperature and increasing body weights. However, a combination of voacanga seed oil and amodiaquine demonstrated an antagonistic effect.