PAN AFRICAN JOURNAL OF LIFE SCIENCES
e-ISSN: 2672-5924
Volume 9, No. 2, August 2025
Pages 547-554
DOI: 10.36108/pajols/5202/90.0271
Pregabalin: Demonstration of Higher Antimalarial Activities Than Artesunate in an Animal Model and Proposed Mechanism of Action
Akeem A. Ayankunle1*, Oyetunji T. Kolawole2, Fadeelah O. Ayankunle3, Olayemi K. Wakeel2, Oyeronke T. Animashaun3, Hazees O. Mohammed1, Fisayo N. Ogunleye1, Isaac D. Asiyanbola1, Olaleye S. Aremu1, Tope G. Atere4, Olusola Ojurongbe5,6 .
1Department of Pharmacology and Therapeutics, College of Health Sciences, Osun State University, Osogbo, Osun State, Nigeria.
2Department of Pharmacology and Therapeutics, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
3Department of Clinical Internship, Homocare Gracious Hospital, Osogbo, Osun State, Nigeria.
4Department of Medical Biochemistry, College of Health Sciences, Osun State University, Osogbo, Osun State, Nigeria.
5Department of Medical Microbiology & Parasitology, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
6Humboldt Research Hub -Center for Emerging & Re-emerging Infectious Diseases (HRH-CERID), Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
ABSTRACT
Background: Sporozoites and merozoites use their surface-bound thrombospondin-related proteins (TRPs) to attach to host-cell hepatocytes and erythrocytes. Blocking these attachments will prevent hepatocytes and erythrocytes from being infected by sporozoites and merozoites, respectively. Pregabalin is approved for the treatment of epilepsy, and it demonstrates antiepileptic effects by blocking neuronal thrombospondin on the α2α2ɗ1 receptor. The evidence showed that TRPs and neuronal thrombospondin share similar structural characteris-tics. Thus, pregabalin may potentially block TRPs. This study compared the antimalarial activity of pregabalin with artesunate and suggested its mechanism of action.
Methods: The curative and suppressive activities were evaluated by administering artesunate, and 12.5, 25, 50 mg/kg of pregabalin (P12.5, P25, P50) to mice infected with ANKA-strain Plasmodium berghei. Parasitemia was determined, and the percentage of chemo-inhibition or chemo-suppression was calculated. Mice were monitored for 28 days to determine the mean survival time. Literature was reviewed to sug-gest the antimalarial action of pregabalin.
Results: In the curative test, artesunate demonstrated a 97.0±1.4%, while P12.5, P25, and P50 showed 88.0±1.7%, 100.0±0.0%, and 100.0±0.0% chemo-inhibition, respectively. Pregabalin demonstrated 100.0±0.0% chemo-suppression at all doses in the suppressive test, compared to 95.7±1.7% shown by artesunate. In the curative study, P25- and P50-treated mice survived for 28±0.0 days, while those treated with P12.5 and artesunate lived for 23.0±0.4 and 26.6±0.7 days, respectively. All mice in the pregabalin-suppressive study survived for 28±0.0 days, compared to 27.0±0.5 days observed in artesunate-treated mice.
Conclusion: Pregabalin demonstrated higher antimalarial activities than artesunate, and blockade of Plasmodium thrombospondin-related proteins could be responsible for its antimalarial action.
Keywords: Pregabalin, artesunate, antimalarial mechanism, Plasmodium berghei, thrombospondin-related proteins