Volume 20, Issue 45, January - June, 2026

Metabolomics of Artemisinin-Based Combination Therapies in experimental animals and humans

Sylvester Aghahowa^1♦, Raymond Ozolua¹, Enitome Bafor¹, Ambrose Isah², Michael Aghahowa³, David Osifo⁴, Philip Obarisiagbon¹, Paul Aikorogie⁵

¹Department of Pharmacology and Toxicology, University of Benin, Nigeria
²Department of Clinical Pharmacology and Therapeutics, University of Benin, Nigeria
³Department of Surgery, College of Health Sciences, Nile University of Nigeria, Abuja, Nigeria
⁴Department of Surgery, College of Medical Sciences University of Benin, Nigeria
⁵Department of Chemical Pathology, University of Benin Teaching Hospital Benin City, Nigeria

^♦Corresponding author
Aghahowa S.E, Department of Pharmacology and Toxicology, University of Benin, Benin City, Nigeria

ABSTRACT

Due to the limited metabolomic data of Artemisinin-Based Combination Therapies (ACTs) in endemic regions, the study assessed the metabolomics of recommended ACTs to understand the pattern of adverse effects in experimental animals (mice, rats, guinea pigs, rabbits) and humans using mass spectrometry. Malaria infection was simulated in all the animal models using Plasmodium berghei NK65, patients who had Plasmodium falciparum infection were also selected. ACTs were administered orally in conventional doses. Serum samples were collected and assayed for metabolomic parameters using standard protocols. The most common metabolites that were significantly altered metabolites in all the models were D-glucose, creatinine, glutamate, aspartate, glycine, taurine, eicosapentaeinoyl-glycerol, hexadecanoic acid, amino-butanoate, and L-tyrosine (OPLS-DA). Commonly altered pathways were lipid, amino acid, carbohydrate, and nucleotide (OPLS-DA). Statistical changes in the values of prediction/correlation in models were 0.77/1 (rats):0.72/0.98 (humans):0.57/1 (guinea pigs):0.27/0.79 (mice):and -0.14/0.54 (rabbits) (OPLS-DA). Sulphadoxine, pyrimethamine, and artemisinin were the commonly expressed drugs significantly in all the models (OPLS-DA). Variations in the values of prediction/correlation of ACTs in humans and animals were (AL ≥ AA > AM > ASP >DHP) and (AL > AA > AM > DHP> ASP): respectively. The annotated metabolomic study had shown that ACTs altered metabolites and metabolic pathways. The results therefore suggest caution in the selection of ACTs in malaria therapy due to possible induction of toxicities.

Keywords: Metabolomics, ACTs, Malaria, Mass spectrometry, Multivariate analysis, Toxicity.

Drug Discovery, 2026, 20(45), e1dd3033

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Published: 03 January 2026