Neuroprotective effect of Hibiscus sabdariffa extract against high glucose-induced toxicity in Neuro-2a cells and Caenorhabditis elegans

Abstract

BACKGROUND: Chronic hyperglycemic conditions can activate aberrant metabolic pathways causing neurotoxicity. OBJECTIVE: This study aimed to explore the effect of ethanol extract of Hibiscus sabdariffa calyxes (HS) against high glucose-induced neurotoxicity in Neuro-2a cells and Caenorhabditis elegans. METHODS: 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 silico approaches for the compounds identified through LC-MS/MS analysis. Further, C. elegans were treated with HS extract in the presence of glucose and analyzed for the neuroprotective effect. RESULTS: 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 A β. CONCLUSION: Our results propose that HS with its active constituents can be considered a promising therapeutic agent to treat hyperglycemia associated neurodegenerative diseases.