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多粘菌素酸和特拉帕松脂从 Trapezifolia Hayne 减少弓形虫生长在人类绒毛外植体,甚至引发抗炎谱。

Polyalthic acid and oleoresin from Copaifera trapezifolia Hayne reduce Toxoplasma gondii growth in human villous explants, even triggering an anti-inflammatory profile.

机构信息

Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Federal University of Uberlândia, Uberlândia, MG, Brazil.

Nucleus of Research in Technological and Exact Sciences, University of Franca, Franca, SP, Brazil.

出版信息

Exp Parasitol. 2023 Jul;250:108534. doi: 10.1016/j.exppara.2023.108534. Epub 2023 Apr 24.

Abstract

Due to the lack of efficient antiparasitic therapy and vaccines, as well as emerging resistance strains, congenital toxoplasmosis is still a public health issue worldwide. The present study aimed to assess the effects of an oleoresin obtained from the species Copaifera trapezifolia Hayne (CTO), and an isolated molecule found in the CTO, ent-polyalthic acid (ent-15,16-epoxy-8(17),13(16),14-labdatrien-19-oic acid) (named as PA), against T. gondii infection. We used human villous explants as an experimental model of human maternal-fetal interface. Uninfected and infected villous explants were exposed to the treatments; the parasite intracellular proliferation and the cytokine levels were measured. Also, T. gondii tachyzoites were pre-treated and the parasite proliferation was determined. Our findings showed that CTO and PA reduced efficiently the parasite growth with an irreversible action, but without causing toxicity to the villi. Also, treatments reduced the levels of IL-6, IL-8, MIF and TNF by villi, what configures a valuable treatment option for the maintenance of a pregnancy in an infectious context. In addition to a possible direct effect on parasites, our data suggest an alternative mechanism by which CTO and PA alter the villous explants environment and then impair parasite growth, since the pre-treatment of villi resulted in lower parasitic infection. Here, we highlighted PA as an interesting tool for the design of new anti-T. gondii compounds.

摘要

由于缺乏有效的抗寄生虫治疗和疫苗,以及新兴的耐药菌株,先天性弓形虫病仍然是全球公共卫生问题。本研究旨在评估从物种 Copaifera trapezifolia Hayne (CTO) 中获得的油树脂,以及在 CTO 中发现的分离分子,即 ent-polyalthic acid (ent-15,16-epoxy-8(17),13(16),14-labdatrien-19-oic acid) (命名为 PA),对 T. gondii 感染的影响。我们使用人绒毛膜绒毛外植体作为人类母胎界面的实验模型。未感染和感染的绒毛外植体暴露于处理中;测量寄生虫细胞内增殖和细胞因子水平。此外,还对 T. gondii 速殖子进行了预处理,并确定了寄生虫的增殖情况。我们的研究结果表明,CTO 和 PA 可有效减少寄生虫的生长,具有不可逆作用,但不会对绒毛造成毒性。此外,治疗还降低了绒毛产生的 IL-6、IL-8、MIF 和 TNF 的水平,这为在感染环境下维持妊娠提供了有价值的治疗选择。除了对寄生虫的直接作用外,我们的数据还表明 CTO 和 PA 改变绒毛外植体环境从而损害寄生虫生长的替代机制,因为绒毛的预处理导致寄生虫感染降低。在这里,我们强调了 PA 作为设计新的抗 T. gondii 化合物的有趣工具。

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