Laboratory of Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará 66075-110, Brazil; National Institute of Science and Technology in Structural Biology and Bioimaging (INCT-INBEB), Rio de Janeiro 21941-901, Brazil.
Laboratory of Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará 66075-110, Brazil.
J Integr Med. 2018 Nov;16(6):404-410. doi: 10.1016/j.joim.2018.08.004. Epub 2018 Aug 25.
In the present study, we evaluated the effects of the aqueous extract of Physalis angulata root (AEPa) on Leishmania infantum proliferation, morphology, and the driving mechanism in leishmanicidal activity and modulatory action on macrophages.
L. infantum promastigotes were treated with 50 and 100 µg/mL AEPa for 72 h and then antipromastigote assay was performed by counts in a Newbauer chamber, morphological changes were analyzed by transmission electron microscopy and the mechanism of the leishmanicidal activity was detected. In addition, macrophages were infected with L. infantum and were used to evaluate anti-amastigote activity of AEPa and effects of AEPa on cytokine secretion after 72-hour treatment.
Treatment with AEPa reduced the numbers of L. infantum promastigotes (50% inhibitory concentration (IC) = 65.9 μg/mL; selectivity index (SI) = 22.1) and amastigotes (IC = 37.9 μg/mL; SI = 38.5) compared with the untreated control. Amphotericin B reduced 100% of the promastigote numbers after 72 h of treatment (IC = 0.2 μg/mL). AEPa induced several morphological changes and increased the production of reactive oxygen species and apoptotic death in promastigotes after treating for 72 h. AEPa (100 μg/mL) promoted tumor necrosis factor-α secretion in macrophages infected with L. infantum after 72 h of treatment, but did not induce an increase in this cytokine in noninfected macrophages. In addition, AEPa showed no cytotoxic effect on J774-A1 cells (50% cytotoxic concentration >1000 μg/mL).
AEPa presented antileishmanial activity against the promastigotes and amastigotes of L. infantum without macrophage cytotoxicity; these results show that natural products such as P. angulata have leishmanicidal potential and in the future may be an alternative treatment for leishmaniasis.
本研究评估了酸浆果根水提物（AEPa）对利什曼原虫增殖、形态以及杀利什曼原虫活性的驱动机制和对巨噬细胞的调节作用。
用 50 和 100μg/mL AEPa 处理利什曼原虫前鞭毛体 72 h，然后通过纽巴氏室计数进行抗前鞭毛体试验，通过透射电子显微镜分析形态变化，并检测杀利什曼原虫活性的机制。此外，用利什曼原虫感染巨噬细胞，并用 AEPa 处理 72 h 后评估 AEPa 的抗内变形虫活性和对细胞因子分泌的影响。
AEPa 处理可减少利什曼原虫前鞭毛体（50%抑制浓度（IC）=65.9μg/mL；选择性指数（SI）=22.1）和内变形虫（IC=37.9μg/mL；SI=38.5）的数量，与未处理的对照组相比。两性霉素 B 处理 72 h 后可减少 100%的前鞭毛体数量（IC=0.2μg/mL）。AEPa 在处理 72 h 后可诱导前鞭毛体发生多种形态变化，并增加活性氧物质的产生和诱导其凋亡死亡。AEPa（100μg/mL）可促进感染利什曼原虫的巨噬细胞分泌肿瘤坏死因子-α，而在未感染的巨噬细胞中不诱导该细胞因子的增加。此外，AEPa 对 J774-A1 细胞无细胞毒性（50%细胞毒性浓度>1000μg/mL）。
AEPa 对利什曼原虫前鞭毛体和内变形虫具有抗利什曼原虫活性，而对巨噬细胞无细胞毒性；这些结果表明，天然产物如酸浆果具有杀利什曼原虫的潜力，未来可能成为利什曼病的一种替代治疗方法。
