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

Primary amoebic meningoencephalitis (PAM), caused by the pathogenic free-living amoeba Naegleria fowleri, 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 com...

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Detalles Bibliográficos
Autores: Zeouk, Ikrame, Sifaoui, Ines, Rizo Liendo, Aitor, Arberas Jiménez, Iñigo, Reyes Batlle, María, López Bazzocchi, Isabel, Bekhti, Khadija, Piñero Barroso, José Enrique, Jiménez Díaz, Ignacio Antonio, Lorenzo Morales, Jacob
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de La Laguna (ULL)
Repositorio:RIULL. Repositorio Institucional de la Universidad de La Laguna
OAI Identifier:oai:riull.ull.es:915/36034
Acceso en línea:http://riull.ull.es/xmlui/handle/915/36034
Access Level:acceso abierto
Palabra clave:Inula viscosa
bioguided fractionation
inuloxin A
brain-eating amoeba
Naegleria fowleri
programmed cell death
Descripción
Sumario:Primary amoebic meningoencephalitis (PAM), caused by the pathogenic free-living amoeba Naegleria fowleri, 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 Inula viscosa (Asteraceae) leaves against N. fowleri trophozoites. Four compounds (1−4) were successfully identified by spectroscopic techniques, but only inuloxin A displayed a potential antiamoebic activity with an IC50 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 in vitro 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.