Mefloquine-curcumin combinations improve host mitochondrial respiration and decrease mitotoxic effects of mefloquine
John Oludele Olanlokun1, Oshireku Wisdom Abiodun1, Adekunle Theophilus Adegbuyi2
1Laboratories for Biomemebrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Current Research in Pharmacology and Drug Discovery
|May 10, 2024
Summary
This study investigated how Plasmodium infection and treatments affect gene expression in mice. Combining mefloquine with curcumin improved therapeutic efficacy and reduced toxicity by modulating key genes.
Area of Science:
- Parasitology and Molecular Biology
- Pharmacology and Toxicology
Background:
- Plasmodium infection poses a significant health challenge, with limited understanding of its impact on host gene expression.
- Existing anti-malarial drugs effectively kill parasites but may have uncharacterized effects on host molecular pathways.
- Investigating gene expression changes during infection and treatment is crucial for understanding malaria pathogenesis and drug mechanisms.
Purpose of the Study:
- To determine the effects of Plasmodium berghei infection and treatments with mefloquine (MF) and curcumin (CM) on host gene expression.
- To evaluate the impact of MF and CM, alone and in combination, on specific genes related to parasite infection and host response.
- To assess the influence of these treatments on glycolysis, toxicity, and antioxidant markers.
Main Methods:
- Plasmodium berghei infection was induced in Swiss mice using chloroquine-susceptible and resistant strains.
- Mice were treated with distilled water, mefloquine, curcumin, or combinations thereof.
- Gene expression analysis (PCR) of FIKK12, AQP3, P38 MAPK, NADH oxidoreductase, and cytochrome oxidase was performed on liver and erythrocyte RNA.
- ELISA assays were used to determine markers of glycolysis, toxicity, and antioxidants.
Main Results:
- Mefloquine alone or combined with curcumin modulated FIKK12 and AQP3 gene expression in both susceptible and resistant malaria models.
- Curcumin reduced P38 MAPK expression, while mefloquine-curcumin treatment restored NADH oxidoreductase and cytochrome oxidase expression suppressed by infection.
- Treatments inhibited glycolysis and toxicity markers, and improved antioxidant systems, with curcumin showing a key role in efficacy and toxicity prevention.
Conclusions:
- Plasmodium infection and anti-malarial treatments significantly modulate host gene expression.
- Combination therapy with mefloquine and curcumin demonstrates enhanced therapeutic efficacy and reduces host toxicity.
- Curcumin plays a vital role in achieving effective treatment outcomes and mitigating adverse effects in malaria.
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