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Vinpocetine increases the microsporicidal effect of albendazole on Encephalitozoon intestinalis
Gülay Sezer1,2, Ülfet Çetinkaya2,3
1Department of Pharmacology, Faculty of Medicine, Erciyes University, 38039 Talas/Kayseri, Türkiye.
Abstract:
Microsporidia are obligate, intracellular, spore-forming eukaryotic fungi that infect humans and animals. In the treatment of disseminated microsporidiosis albendazole is the choice of drug. In recent years, antiparasitic activity of phosphodiesterase (PDE) enzyme inhibitors has been demonstrated against parasites and fungi, however, there is no information on microsporidia. Vinpocetine is currently used as a cerebral vasodilator drug and also as a dietary supplement to improve cognitive functions. Vinpocetine inhibits PDE1, so we aimed to investigate whether vinpocetine alone or in combination with albendazole has any effect on the spore load of Encephalitozoon intestinalis (E. intestinalis)-infected HEK293 cells. After determining the noncytotoxic concentrations of vinpocetine and albendazole on the host cell by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, HEK293 cells were infected with E. intestinalis spores. Then, two different concentrations of vinpocetine, albendazole, and a combination of both drugs were applied to the cells with an interval of 72 h for 15 days. Spore load of the cells was analyzed by real-time PCR. After the last treatment, spore Deoxyribonucleic Acid (DNA) load was significantly reduced only in the group treated with 14 ng/ml albendazole. It was not different from control in groups treated with 7 ng/ml albendazole and 4-20 µM vinpocetine. However, the combination of vinpocetine significantly increased the effect of albendazole at both concentrations. To our knowledge, this is the first study to investigate the microsporicidal activity of vinpocetine as well as its combinations with albendazole. However, further studies are needed to investigate the mechanism of action and also confirm in vivo conditions.
Insights
Vinpocetine combined with albendazole shows promise in reducing microsporidia spore load. This study is the first to explore vinpocetine
Area of Science:
- Mycology
- Parasitology
- Pharmacology
Background:
- Microsporidia are opportunistic fungal pathogens causing disseminated infections in humans and animals.
- Albendazole is the primary treatment for disseminated microsporidiosis.
- Phosphodiesterase (PDE) inhibitors exhibit antiparasitic and antifungal activities, but their effect on microsporidia is unknown.
Purpose of the Study:
- To investigate the efficacy of vinpocetine, a PDE1 inhibitor, alone and in combination with albendazole against Encephalitozoon intestinalis (E. intestinalis).
- To determine the effect on the spore load in infected HEK293 cells.
Main Methods:
- Non-cytotoxic concentrations of vinpocetine and albendazole were determined using MTT assay.
- HEK293 cells were infected with E. intestinalis spores.
- Cells were treated with varying concentrations of vinpocetine, albendazole, or their combination over 15 days, with spore load quantified by real-time PCR.
Main Results:
- Albendazole (14 ng/ml) significantly reduced spore DNA load.
- Vinpocetine (4-20 µM) alone did not significantly alter spore load compared to controls.
- Combination therapy significantly enhanced albendazole's microsporicidal effect at both tested concentrations.
Conclusions:
- Vinpocetine potentiates the efficacy of albendazole against E. intestinalis.
- This is the first study demonstrating the potential microsporicidal activity of vinpocetine in combination therapy.
- Further in vivo studies are required to validate these findings and elucidate the mechanism of action.
