Unveiling the antimalarial properties of Terminalia ivorensis (A. Chev) stem bark aqueous extract: In vivo efficacy testing and in silico predictions

Due to the spreading resistance to antimalarial drugs, new therapeutics are urgently needed, preferably with novel modes of action. Extracts from Terminalia ivorensis have previously been shown to possess activity in vitro against multidrug-resistant and drug-sensitive strains of Plasmodium falciparum. However, to the best of our knowledge, no scientific study has been published describing the antimalarial potential of these extracts through in vivo efficacy testing. This study aimed to determine the safety and antimalarial efficacy of the T. ivorensis stem bark aqueous extract (TiH2O) in a mouse model using the OECD 423 protocol and the suppressive and curative murine malaria models, and to predict in silico the pharmacokinetic properties and drug-likeness of two major phytochemical constituents. The in vivo antimalarial efficacy was assessed using the P. berghei NK65-infected mice. The TiH2O treatment impact on biochemical parameters was measured using established standard procedures. The pharmacokinetics prediction was achieved through the pkCSM predictor and Swiss ADME. The TiH2O extract was nontoxic in BALB/c mice at a lethal dose of 50 (LD50) > 2000 mg/kg. The TiH2O extract displayed strong antimalarial efficacy with 100% parasitemia suppression at 200 mg/kg b.w. after 4 days of treatment while its oral administration at 400 mg/kg b.w. in the curative model significantly decreased P. berghei parasitemia by 94.07% with a median efficacy dose (ED50) of 96.80 mg/kg. The administration of TiH2O extract restored the histological parameters disrupted by P. berghei, and the transaminase (ALT and AST) activity, creatinine, and bilirubin levels significantly decreased compared to the negative control mice. In silico explorations showed that the main constituents leucodelphidin (leucodelphinidin) and ellagic acid of the TiH2O extract have drug-like properties, thus indicating that T. ivorensis might constitute a promising source of antimalarial chemical entities with good pharmacokinetics and drug-like properties. The results obtained further corroborated the preliminary in vitro antiplasmodial studies of T. ivorensis stem bark aqueous extract. The metabolome of TiH2O extract should be further profiled in the prospects of characterizing novel natural product scaffolds to support antimalarial drug discovery

In Vivo Antiplasmodial Activity of Terminalia mantaly Stem Bark Aqueous Extract in Mice Infected by Plasmodium berghei

Background. Terminalia mantaly is used in Cameroon traditional medicine to treat malaria and related symptoms. However, its antiplasmodial efficacy is still to be established. Objectives. The present study is aimed at evaluating the in vitro and in vivo antiplasmodial activity and the oral acute toxicity of the Terminalia mantaly extracts. Materials and Methods. Extracts were prepared from leaves and stem bark of T. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screened in vitro against the chloroquine-resistant strain W2 of P. falciparum to confirm its in vitro activity, and the most potent one was assessed in malaria mouse model at three concentrations (100, 200, and 400 mg/kg/bw). Biochemical, hematological, and histological parameters were also determined. Results. Overall, 7 extracts showed in vitro antiplasmodial activity with IC50 ranging from 0.809 μg/mL to 5.886 μg/mL. The aqueous extract from the stem bark of T. mantaly (Tmsbw) was the most potent (IC50=0.809 μg/mL) and was further assessed for acute toxicity and efficacy in Plasmodium berghei-infected mice. Tmsbw was safe in mice with a median lethal dose (LD50) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacy in vivo with ED50 of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters. Conclusion. The results suggest that the stem bark extract of T. mantaly possesses antimalarial activity