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探讨从()中分离出的菊粉 A 通过激活细胞程序性死亡对食脑变形虫的抗感染价值。

Exploring the Anti-Infective Value of Inuloxin A Isolated from against the Brain-Eating Amoeba () by Activation of Programmed Cell Death.

机构信息

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, Islas Canarias 38203, Spain.

Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), https://www.ricet.es/.

出版信息

ACS Chem Neurosci. 2021 Jan 6;12(1):195-202. doi: 10.1021/acschemneuro.0c00685. Epub 2020 Dec 9.

Abstract

Primary amoebic meningoencephalitis (PAM), caused by the pathogenic free-living amoeba , is a rare but fatal disease. Nowadays, no fully effective therapy is available to erradicate or prevent this disease. Natural products could constitute a promising source of useful bioactive compounds in drug discovery. The present study is a characterization of main active compounds from the ethanolic extract of (Asteraceae) leaves against trophozoites. Four compounds (-) were successfully identified by spectroscopic techniques, but only inuloxin A displayed a potential antiamoebic activity with an IC of 21.27 μM. The specificity of this compound toward the studied strain leads us to analyze the insight into its mechanism of action by performing assays of programmed cell death markers and to discuss the structure-activity relationship (SAR). The obtained results demonstrated that inuloxin A interferes with various processes leading to membrane damage, mitochondria alteration, chromatin condensation, and ROS accumulation, which highlight features specific to apoptosis. The current findings could be a promising step for developing new effective drugs against PAM.

摘要

原发性阿米巴脑膜脑炎(PAM)是由致病性自由生活的阿米巴引起的一种罕见但致命的疾病。目前,尚无完全有效的疗法可以根除或预防这种疾病。天然产物可能是药物发现中有用生物活性化合物的有前途的来源。本研究对(菊科)叶乙醇提取物中的主要活性化合物进行了表征,以对抗滋养体。通过光谱技术成功鉴定了四种化合物(-),但只有菊苣素 A 表现出潜在的抗阿米巴活性,IC 为 21.27 μM。该化合物对研究菌株的特异性使我们能够通过进行程序性细胞死亡标志物的分析来探讨其作用机制,并讨论结构-活性关系(SAR)。获得的结果表明,菊苣素 A 干扰导致膜损伤、线粒体改变、染色质浓缩和 ROS 积累的各种过程,这突出了凋亡的特异性特征。目前的研究结果可能是开发针对 PAM 的新型有效药物的有希望的一步。

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