title: In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi-Synthetic Spirosteroid Analogues.
abstract: Two spirosteroid analogues were synthesized and evaluated for their in vitro neuroprotective activities in PC12 cells, against glutamate-induced excitotoxicity and mitochondrial damage in glucose deprivation conditions, as well as their anti-inflammatory potential in LPS/IFNγ-stimulated microglia primary cultures. We also evaluated the in vitro anti-excitotoxic and anti-inflammatory activities of natural and endogenous steroids. Our results show that the plant-derived steroid solasodine decreased PC12 glutamate-induced excitotoxicity, but not the cell death induced by mitochondrial damage and glucose deprivation. Among the two synthetic spirosteroid analogues, only the (25R)-5α-spirostan-3,6-one (S15) protected PC12 against ischemia-related in vitro models and inhibited NO production, as well as the release of IL-1β by stimulated primary microglia. These findings provide further insights into the role of specific modifications of the A and B rings of sapogenins for their neuroprotective potential.
authors.affiliation: Centro de Investigaci&#243;n y Desarrollo de Medicamentos (CIDEM), Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600 La Habana, Cuba. laura.garcia@cidem.cu.
authors.forename: Laura
authors.initials: L
authors.lastname: García-Pupo
authors.affiliation: Centro de Estudios de Productos Naturales, Facultad de Qu&#237;mica, Universidad de la Habana, Zapata s/n entre G y Carlitos Aguirre, Vedado, Plaza de la Revoluci&#243;n, CP 10400 La Habana, Cuba. zaldo@fq.uh.cu.
authors.forename: Armando
authors.initials: A
authors.lastname: Zaldo-Castro
authors.affiliation: Natural Products &amp; Food Research &amp; Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, PC 2610 Antwerp, Belgium. vasiliki.exarchou@uantwerpen.be.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Exarchou
authors.affiliation: Centro de Estudios de Productos Naturales, Facultad de Qu&#237;mica, Universidad de la Habana, Zapata s/n entre G y Carlitos Aguirre, Vedado, Plaza de la Revoluci&#243;n, CP 10400 La Habana, Cuba. jetacoronte@yahoo.com.
authors.forename: Juan Enrique
authors.initials: JE
authors.lastname: Tacoronte-Morales
authors.affiliation: Natural Products &amp; Food Research &amp; Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, PC 2610 Antwerp, Belgium. luc.pieters@uantwerpen.be.
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
authors.affiliation: Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, PC 2610 Antwerp, Belgium. wim.vandenberghe@uantwerpen.be.
authors.forename: Wim
authors.initials: W
authors.lastname: Vanden Berghe
authors.affiliation: Centro de Investigaci&#243;n y Desarrollo de Medicamentos (CIDEM), Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600 La Habana, Cuba. yanier.nunez@cidem.cu.
authors.forename: Yanier
authors.initials: Y
authors.lastname: Nuñez-Figueredo
authors.affiliation: Centro de Estudios Investigaciones y Evaluaciones Biol&#243;gicas (CEIEB), Instituto de Farmacia y Alimentos (IFAL), Universidad de la Habana, Calle 222 #2317/23 y 31 La Coronela, La Lisa, CP 13600 La Habana, Cuba. rdelgado@infomed.sld.cu.
authors.forename: René
authors.initials: R
authors.lastname: Delgado-Hernández
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D005260:Female; D053583:Interleukin-1beta / Q000096:biosynthesis; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D016716:PC12 Cells; D051381:Rats; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D013141:Spiro Compounds; D013256:Steroids; D009569:Nitric Oxide
keywords: excitotoxicity; inflammatory mediators; neuroprotection; spirosteroids