In silico, in vitroandin vivoantiplasmodial activity of β-amyrin and its potential synergistic effect when co-administered with artesunate

Abstract ID 91566 Poster Board 080 Malaria presents a serious health concern worldwide. Combination therapy has been adopted to curb the development of resistance, and this calls for the urgent search for newer drug candidates to be used either in new drug combination therapies or as replacements for one of the already existing combinations. The objective of this study was to examine the antimalarial properties of β-amyrin, a triterpenoid compound that is naturally present in the root bark of Zizizphus abyssinica, an African medicinal plant. Also, the compound's possible synergistic activity when co-administered with artesunate was investigated. To begin with, the potential antiplasmodial targets of β-amyrin were first examined in silico, and then its in vitro antiplasmodial activity against a multidrug-resistant strain of Plasmodiumfalciparum (Pf), Dd2 and in vivo activity in mice infected with Plasmodiumberghei ANKA (PbA) were accessed. The molecular modeling studies indicated that Plasmodium falciparum hexose transporter (PfHT1) is a possible target for β-amyrin. Molecular dynamics simulation indicated that β-amyrin forms a stable complex with PfHT1. Furthermore, β-amyrin exhibited potent antiplasmodial activity against Dd2 in vitro with an IC₅₀ of 13.81 ± 1.070 μg/mL and its ED₅₀ in mice infected with PbA was 16.97 ± 1.11 mg/kg. It is worth noting that isobolgraphic analysis of β-amyrin and artesunate revealed a synergistic effect with a theoretical ED₅₀ (Zadd) of 9.37 ± 1.6 mg/kg, experimental ED₅₀ (Zexp) of 2.23 ± 1.2 mg/kg and interaction index of 0.24. More importantly, β-amyrin, with or without artesunate, significantly reduced weight loss, offered protection against liver injury and increased the survival of infected mice. β-amyrin is a promising antimalarial agent with potent activities against Dd2 in vitro and PbA in vivo, and can provide synergistic effect when co-administrated with artesunate. This work was funded by the Directorate of Research, Innovation and Consultancy - University of Cape Coast (DRIC-UCC) [RSG/GRP/COHAS/2020/132].