Chemotherapeutic Interaction of Vernonia amygdalina (Delile) Leaf Extract with Artesunate and Amodiaquine in Murine Malaria Model

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.

Antimalarial herbal drugs: a review of their interactions with conventional antimalarial drugs

“…The study revealed a significant increase in the chemosuppressive effect of AQ and ART, as well as parasite clearance when co-administered with VA extract. Also, the mean survival period was higher in animals that received the three combinations, VA, AQ, AR compared to placebo [3].…”

“…Prior to the emergence of resistance, CQ was an efficient and affordable antimalarial drug of choice [9,13]. However, artemisinin and its semisynthetic derivatives produced better effectiveness than quinine [14] and this led to the recommendation of artemisinin and its derivatives, artemisinin-based combination therapy (ACTs) as current first-line drugs against malaria caused by P. falciparum infection [3,10]. Notwithstanding the recommendation of the ACTs as current antimalarial frontline therapy in most tropical countries, artemisinin-resistant Plasmodium parasites still prevail in some parts of the world [6,13], and this calls for more researches on more effective and safer alternatives.…”

“…The practice of concomitant application of conventional antimalarial drugs and herbal antimalarial drugs is not only limited to the poor and uneducated, but the rich and the learned are also involved [20]. Indeed, these practices have their therapeutic implications, as pharmacokinetics or pharmacodynamics interactions of such drugs could be antagonistic, additive or synergistic [3]. However, the emerging clinical impact of Pharmacists through the due Pharmaceutical care process recommends hope with positive patients' outcome [21].…”

“…Researchers, knowing the implications of herb-drug interactions with respect to increasing rates of combination of herbal remedies with conventional antimalarial drugs have taken responsibilities to unravel the possible effects that could result from such interaction. It is also obvious that the potential interaction of conventional drugs with herbs is rarely given important attention by most Physicians [3,11,13]. Some researchers have reviewed interactions between herbs and conventional drugs [22] but none have specifically looked into antimalarial herbal remedies and conventional antimalarial drugs as is attempted in this review.…”

“…Although significant achievements have been made contending malaria, it has become worrisome following discovery of the resistance strains of P. falciparum against artemisinin combination therapies (ACTs), the prominent antimalarial agents [3].…”