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

Mariscal Brice Tchatat Tali; Eugenie Aimée Madiesse Kemgne; Cedric Derick Jiatsa Mbouna; Marius Jaures Tsakem Nangap; Aubin Youbi Kamche; Souleyman Hassan; Jean Claude Tchouankeu; Fabrice Fekam Boyom

doi:10.62313/ijpbp.2024.194

Authors

Mariscal Brice Tchatat Tali University of Yaoundé 1, Faculty of Science, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Antimicrobial and Biocontrol Agents Unit, P.O. Box 812, Yaoundé, Cameroon https://orcid.org/0000-0002-3003-5234
Eugenie Aimée Madiesse Kemgne Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaounde, Cameroon https://orcid.org/0009-0009-4455-4738
Cedric Derick Jiatsa Mbouna University of Yaoundé 1, Faculty of Science, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Antimicrobial and Biocontrol Agents Unit, P.O. Box 812, Yaoundé, Cameroon https://orcid.org/0000-0002-9501-6958
Marius Jaures Tsakem Nangap University of Yaoundé 1 Department of Animal Biology and Physiology, P.O. Box 812, Yaounde, Cameroon https://orcid.org/0009-0007-2327-6914
Aubin Youbi Kamche University of Yaoundé 1, Faculty of Science, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Antimicrobial and Biocontrol Agents Unit, P.O. Box 812, Yaoundé, Cameroon https://orcid.org/0009-0001-4061-2912
Souleyman Hassan University of Yaoundé 1, Faculty of Science, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Antimicrobial and Biocontrol Agents Unit, P.O. Box 812, Yaoundé, Cameroon https://orcid.org/0000-0002-2928-8613
Jean Claude Tchouankeu University of Yaoundé 1, Faculty of Science, Laboratory of Natural Products and Organic Synthesis, P.O. Box 812, Yaoundé, Cameroon https://orcid.org/0000-0002-5202-0316
Fabrice Fekam Boyom Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaounde, Cameroon https://orcid.org/0000-0002-3147-364X

DOI:

https://doi.org/10.62313/ijpbp.2024.194

Keywords:

Malaria, Terminalia ivorensis, Drug efficacy, Plasmodium berghei, Biochemical markers, ADMET prediction

Abstract

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.

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