Hibiscus sabdariffa extract protects HT-22 cells from glutamate-induced neurodegeneration by upregulating glutamate transporters and exerts lifespan extension in C. elegans via DAF-16 mediated pathway

BACKGROUND: Glutamate toxicity is involved in several neurodegenerative conditions, including Alzheimer’s disease. OBJECTIVE: The study aims to investigate the neuroprotective efficacy of ethanol extract Hibiscus sabdariffa calyces (HS) against glutamate-induced HT-22 cells and anti-aging property Caenorhabditis elegans. METHODS: were pre-treated with HS followed by glutamate evaluated for effect using cell viability assay, confocal microscopic analysis, qPCR, Western blot, docking analysis. Induction C. elegans was analyzed through physiological assays qPCR RESULTS: GC-MS analysis showed presence 19 compounds antioxidant properties oleamide, 2-(diethoxymethyl)furan 5-methylfurfural. In vitro studies reveal that exerted inducing oxidative stress, depleting glutathione, downregulating transporters, genes, autophagy (Beclin-1, Atg-5, Atg-7, LC3-II) activation MAPK (p38, JNK) pathway, causing apoptosis. However, pre-treatment (5, 10μg/ml) reversed offered neuroprotection. silico can bind effectively inhibit activity NMDAR, calpain-1 GSK-3β. elegans, extended lifespan, reduced accumulation lipofuscin, modulated healthspan-related genes downregulated expression daf-2. CONCLUSION: Our results indicate its bioactive components exhibits upregulating inhibiting exerts DAF-16 dependent mechanism.