부산대학교 도서관

Chronic hyperglycemic conditions can activate aberrant metabolic pathways causing neurotoxicity. This study aimed to explore the effect of ethanol extract of Hibiscus sabdariffacalyxes (HS) against high glucose-induced neurotoxicity in Neuro-2a cells and Caenorhabditis elegans. To ascertain the neuroprotective effect, Neuro-2a cells were pre-treated with HS followed by high glucose and assessed for cell viability, reactive oxygen species (ROS) generation, alterations in mitochondrial membrane potential (ΔΨm) using confocal microscopy, Real-Time PCR, Western blot and in silicoapproaches for the compounds identified through LC-MS/MS analysis. Further, C. eleganswere treated with HS extract in the presence of glucose and analyzed for the neuroprotective effect. High glucose exhibited toxicity in Neuro-2a cells by ROS generation, disrupting ΔΨm, modulating stress response and lipid metabolism genes, altering signaling proteins (AKT, JNK), and apoptosis (P53, Caspase-3). However, pre-treatment with HS extract reversed the effect and exhibited neuroprotection. Compounds including allo-Aromadendrene, and N-Feruloyltyramine were identified through LC-MS/MS analysis. Docking studies against candidate protein targets indicated that the compounds of HS extract exhibit higher docking scores and can inhibit/activate the targets. Further, HS extended the lifespan of C. elegans(CL2006) from high glucose toxicity through the downregulation of Aβ. Our results propose that HS with its active constituents can be considered a promising therapeutic agent to treat hyperglycemia associated neurodegenerative diseases.