Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil.
Laboratory of Biology of Reproduction, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil.
Front Cell Infect Microbiol. 2023 Feb 13;13:1113896. doi: 10.3389/fcimb.2023.1113896. eCollection 2023.
The conventional treatment of congenital toxoplasmosis is mainly based on the combination of sulfadiazine and pyrimethamine. However, therapy with these drugs is associated with severe side effects and resistance, requiring the study of new therapeutic strategies. There are currently many studies with natural products, including oleoresin, showing actions against some pathogens, as and . In the present study, we investigated the effects of the leaf hydroalcoholic extract and oleoresin from against in human villous (BeWo) and extravillous (HTR8/SVneo) trophoblast cells, as well as in human villous explants from third-trimester pregnancy. For this purpose, both cells and villous explants were infected or not with , treated with hydroalcoholic extract or oleoresin from and analyzed for toxicity, parasite proliferation, cytokine and ROS production. In parallel, both cells were infected by tachyzoites pretreated with hydroalcoholic extract or oleoresin, and adhesion, invasion and replication of the parasite were observed. Our results showed that the extract and oleoresin did not trigger toxicity in small concentrations and were able to reduce the intracellular proliferation in cells previously infected. Also, the hydroalcoholic extract and oleoresin demonstrated an irreversible antiparasitic action in BeWo and HTR8/SVneo cells. Next, adhesion, invasion and replication of were dampened when BeWo or HTR8/SVneo cells were infected with pretreated tachyzoites. Finally, infected and treated BeWo cells upregulated IL-6 and downmodulated IL-8, while HTR8/SVneo cells did not change significantly these cytokines when infected and treated. Finally, both the extract and oleoresin reduced the proliferation in human explants, and no significant changes were observed in relation to cytokine production. Thus, compounds from presented different antiparasitic activities that were dependent on the experimental model, being the direct action on tachyzoites a common mechanism operating in both cells and villi. Considering all these parameters, the hydroalcoholic extract and oleoresin from can be a target for the establishment of new therapeutic strategy for congenital toxoplasmosis.
先天性弓形虫病的传统治疗主要基于磺胺嘧啶和乙胺嘧啶的联合用药。然而,这些药物的治疗与严重的副作用和耐药性有关,需要研究新的治疗策略。目前有许多关于天然产物的研究,包括[油树脂],表明其对一些病原体具有作用,如[和]。在本研究中,我们研究了来自[的]叶水醇提取物和油树脂对人绒毛(BeWo)和绒毛外(HTR8/SVneo)滋养层细胞以及来自妊娠晚期的人绒毛外植体中的[的作用。为此,用[感染或不感染]感染两种细胞和绒毛外植体,用水醇提取物或油树脂处理,分析毒性、寄生虫增殖、细胞因子和 ROS 产生。同时,用预处理的速殖子感染两种细胞,并观察寄生虫的黏附、侵袭和复制。我们的结果表明,在小浓度下,提取物和油树脂不会引发毒性,并能减少先前感染的细胞中的[内增殖。此外,水醇提取物和油树脂在 BeWo 和 HTR8/SVneo 细胞中表现出对寄生虫的不可逆抗寄生虫作用。接下来,当 BeWo 或 HTR8/SVneo 细胞感染预处理的速殖子时,[的黏附、侵袭和复制受到抑制。最后,感染和处理的 BeWo 细胞上调了 IL-6,下调了 IL-8,而 HTR8/SVneo 细胞在感染和处理时这些细胞因子没有明显变化。最后,提取物和油树脂都减少了人外植体中的[增殖,细胞因子产生没有明显变化。因此,来自[的]化合物表现出不同的抗寄生虫活性,这取决于实验模型,速殖子的直接作用是在两种细胞和绒毛中起作用的共同机制。考虑到所有这些参数,[的]水醇提取物和油树脂可以作为先天性弓形虫病新治疗策略的目标。