Abstract
Aim of the Study: Conventional antimalarial drugs are used concurrently with herbal remedies in malarial endemic developing countries. Vernonia amygdalina is one of such popular herbs used in the treatment of malaria. This study aimed at investigating the antimalarial chemotherapeutic interaction of Vernonia amygdalina (VA) when combined with Amodiaquine (AQ) and/or Artesunate (AS) in a murine Plasmodium berghei malaria model.
 Methodology: Various doses of aqueous VA leaf extract (100-500 mg/kg/day), AQ (2-10 mg/kg/day) and AS (0.8-4 mg/kg/day) were administered orally to P berghei.-infected Swiss albino mice to determine their sub-therapeutic doses. These doses were subsequently used to investigate the chemotherapeutic interactions of VA with AQ and/or AS in both early and established malaria infection test models. The survival of animals with established infections that received different drug/herb treatments were determined using their mean survival time (days) and Kaplan-Meier survival curves (percentage). Using GraphPad Instat (version 3.10) and PrismR (version 5.01) the data obtained were subjected to One-way ANOVA, followed by Student-Newman-Keuls test. P < .05 was considered statistically significant.
 Results: The sub-therapeutic doses of VA, AQ and AS were found to be 100 mg/kg, 2 mg/kg and 2.4 mg/kg, respectively. The chemosuppressive effect of AQ or AS was significantly increased (p< 0.05) when administered in combination with the VA extract. Similarly, combination of VA extract with AQ or AS resulted in significant (P < .05) parasite clearance when compared to the effects of the herb or the conventional drugs administered separately. The mean survival period of animals with established infection was also significantly enhanced by the VA alone or with AQ (or AS) compared to placebo.
Highlights
World Malaria Report (2018) documented that malaria is most prevalent in tropical countries involving over 219 million cases and 435,000 estimated deaths, with high vulnerability being among children under five and pregnant women [1]
The antimalarial effects of different doses of V. amygdalina (VA), amodiaquine (AQ) and artesunate (AS) on parasite density on days 4 and 7 post-treatment are presented in Tables 1, 2 and 3, respectively
The sub-therapeutic doses of VA, AQ and AS were found to be 100 mg/kg, 2 mg/kg and 2.4 mg/kg, respectively. These subtherapeutic doses were used to assess the chemotherapeutic interaction of V. amygdalina with the conventional antimalarial drugs in subsequent combination treatments
Summary
World Malaria Report (2018) documented that malaria is most prevalent in tropical countries involving over 219 million cases and 435,000 estimated deaths, with high vulnerability being among children under five and pregnant women [1]. The advocacy for Artemisinin-Based Combination Therapies (ACTs) such as artesunateamodiaquine as the standard practice in malaria chemotherapy, has globally reduced estimates of malaria cases and related deaths [2]. The detection of resistance of P. falciparum to artemisinin in Southeast Asia, is threatening the gains recorded in combating malaria [1]. This worrisome emergence of P. falciparum resistance at the Cambodia-Thailand border has raised the possibility that malaria parasites strains that are resistant to ACTs and other combination therapies may have evolved [3]. The need to explore novel antimalarial drugs has become a necessity due to the alarming rate at which P. falciparum has developed resistance to old antimalarial drugs as well as other newer synthetic antimalarial drugs [4]
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