微孢子虫是专性的,细胞内,孢子形成的真核真菌,感染人类和动物。在播散性微孢子虫病的治疗中,阿苯达唑是药物的选择。近年来,已经证明了磷酸二酯酶(PDE)抑制剂对寄生虫和真菌的抗寄生虫活性,然而,没有关于微孢子虫的信息。长春西汀目前用作脑血管扩张剂药物,也用作改善认知功能的膳食补充剂。长春西汀抑制PDE1,因此我们旨在研究长春西汀单独或与阿苯达唑联合使用是否对头孢菌素肠的孢子负荷有任何影响(E.肠)感染的HEK293细胞。MTT法测定长春西汀和阿苯达唑在宿主细胞上的非细胞毒性浓度,用大肠杆菌孢子感染HEK293细胞。然后,两种不同浓度的长春西汀,阿苯达唑,将两种药物的组合以72小时的间隔应用于细胞,持续15天。通过实时PCR分析细胞的孢子负载。在最后一次治疗之后,仅在用14ng/mL阿苯达唑处理的组中,孢子DNA载量显着降低。在使用7ng/mL阿苯达唑和4-20µM长春西汀治疗的组中,与对照组没有差异。然而,长春西汀的组合在两种浓度下均显着增加了阿苯达唑的作用。据我们所知,这是首次研究长春西汀及其与阿苯达唑的组合的杀微孢子活性。然而,需要进一步的研究来研究作用机制,并确认体内条件。
E.肠肌,人类微孢子虫相关疾病的常见原因,阿苯达唑用于治疗肠球菌感染,长春西汀抑制PDE1和电压门控Ca2+通道,长春西汀能显著增强阿苯达唑对大肠杆菌孢子DNA载量的影响。
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.
Encephalitozoon intestinalis, a common cause of microsporidia-associated diseases in humans, albendazole is used in the treatment of E. intestinalis infection, vinpocetine inhibits PDE1 and voltage-gated Ca2+ channels, vinpocetine significantly enhances the effect of albendazole on E. intestinalis spore DNA load.