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首页> 外文期刊>The American Journal of Tropical Medicine and Hygiene >Vismione B Interferes with Trypanosoma cruzi Infection of Vero Cells and Human Stem Cell-Derived Cardiomyocytes
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Vismione B Interferes with Trypanosoma cruzi Infection of Vero Cells and Human Stem Cell-Derived Cardiomyocytes

机译:Vismione B干扰了睾丸瘤Cruzi感染Vero细胞和人干细胞衍生的心肌细胞

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Traditional African medicine is a source of new molecules that might be useful in modern therapeutics. We tested ten limonoids, six quinones, one xanthone, one alkaloid, and one cycloartane, isolated from four Cameroonian medicinal plants, and one plant-associated endophytic fungus, against Trypanosoma cruzi, the etiological agent of Chagas disease (CD). Vero cells, or human-induced pluripotent stem cells (hiPSC)-derived cardiomyocytes (hiPSC-CM) were infected with T. cruzi trypomastigotes (discrete typing unit types I or II). Infection took place in the presence of drugs, or 24 hours before drug treatment. Forty-eight hours after infection, infection rates and parasite multiplication were evaluated by Giemsa stain. Cell metabolism was measured to determine functional integrity. In Vero cells, several individual molecules significantly affected T. cruzi infection and multiplication with no, or minor, effects on cell viability. Reduced infection rates and multiplication by the quinone vismione B was superior to the commonly used therapeutic benznidazole (BNZ). The vismione B concentration inhibiting 50% of T. cruzi infection (IC50) was 1.3 mu M. When drug was applied after infection, anti-Trypanosoma effects of vismione B [10 mu M) were significantly stronger than effects of BNZ (23 mu M). Furthermore, in hiPSC-CM cultures, infection and multiplication rates in the presence of vismione B (10 mu M) were significantly lower than in BNZ (11.5 mu M), without showing signs of cytotoxicity. Our data indicate that vismione B is more potent against T. cruzi infection and multiplication than BNZ, with stronger effects on established infection. Vismione B, therefore, might become a promising lead molecule for treatment development for CD.
机译:传统的非洲医药是新分子的来源,可能在现代治疗中有用。我们测试了10个唇膏,六个醌,一种X吨酮,一个生物碱和一个环丙烷,从四个喀麦隆药用植物中分离出来,以及一种植物相关的内生真菌,对抗锥瘤瘤Cruzi,Chagas疾病的病因(CD)。 Vero细胞或人诱导的多能干细胞(HIPSC)的心肌细胞(HIPSC-CM)被T.Cruzi Trypomastigotes(离散键入单元类型I或II)感染。感染在药物存在下进行,或药物治疗前24小时。感染后四十八小时,通过Giemsa染色评估感染率和寄生虫倍增。测量细胞代谢以确定功能完整性。在VERO细胞中,几种单独的分子显着影响T.Cruzi感染和繁殖,没有对细胞活力的影响。醌vismioneb的感染率降低和乘法优于常用的治疗苯并唑(BNZ)。 Vismione B浓度抑制50%的T.Cruzi感染(IC50)为1.3亩。当药物被感染后,Vismione B [10μm)的抗锥体瘤作用明显强于BNZ的影响(23亩)。此外,在Vismione B(10μm)存在下的髋关节-CM培养物中,感染和繁殖率显着低于BNZ(11.5μm),而不显示细胞毒性的迹象。我们的数据表明,Vismione B对T.Cruzi感染和比BNZ繁殖更有效,对既定感染有较强的影响。因此,Vismione B可能成为CD处理发育的有前途的铅分子。

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