In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi-Synthetic Spirosteroid Analogues
Laura García-Pupo,
Armando Zaldo-Castro,
Vassiliki Exarchou,
Juan Enrique Tacoronte-Morales,
Luc Pieters,
Wim Vanden Berghe,
Yanier Nuñez-Figueredo,
René Delgado-Hernández
Affiliations
Laura García-Pupo
Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600 La Habana, Cuba
Armando Zaldo-Castro
Centro de Estudios de Productos Naturales, Facultad de Química, Universidad de la Habana, Zapata s/n entre G y Carlitos Aguirre, Vedado, Plaza de la Revolución, CP 10400 La Habana, Cuba
Vassiliki Exarchou
Natural Products & Food Research & Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, PC 2610 Antwerp, Belgium
Juan Enrique Tacoronte-Morales
Centro de Estudios de Productos Naturales, Facultad de Química, Universidad de la Habana, Zapata s/n entre G y Carlitos Aguirre, Vedado, Plaza de la Revolución, CP 10400 La Habana, Cuba
Luc Pieters
Natural Products & Food Research & Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, PC 2610 Antwerp, Belgium
Wim Vanden Berghe
Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, PC 2610 Antwerp, Belgium
Yanier Nuñez-Figueredo
Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600 La Habana, Cuba
René Delgado-Hernández
Centro de Estudios Investigaciones y Evaluaciones Biológicas (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
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.
