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/IFN?-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)-5?-spirostan-3,6-one (S15) protected PC12 against ischemia-related in vitro models and inhibited NO production, as well as the release of IL-1? 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.

SUBMITTER: Garcia-Pupo L 

PROVIDER: S-EPMC6274191 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature