Neuroprotective effect of Annona muricata-derived polysaccharides in neuronal HT22 cell damage induced by hydrogen peroxide

Crude extracts and phytochemical compounds derived from Annona muricata leaves have been demonstrated to exert neuroprotective effects. However, the neuroprotective effects of Annona muricata leaves-derived polysaccharide extracts (ALPs) have not been investigated. ALP treatment was shown to induce concentration-dependent antioxidant activity in HT22 cells, and to increase cell viability in H 2 O 2 -treated HT22 cells. These effects were correlated with a decrease in major components of oxidation, including: Ca 2+ , ROS, and malondialdehyde (MDA). Mediators of the intracellular response to oxidation, including Bax, cytochrome c, and cleaved caspases-3, -8, -9, MAPKs, and NF-κB, were positively influenced by ALP treatment under conditions of H 2 O 2 -mediated oxidative stress. In addition, ALP restored the expression of superoxide dismutase (SOD) and associated signaling pathways (PARP, PI3K/AKT and Nrf2-mediated HO-1/NQO-1) following H 2 O 2 treatment. These results provide new pharmacological evidence that ALP facilitates neuroprotection via prevention of neuronal oxidative stress and promotion of cell survival signaling pathways. ABTS: 2,2ʹ-azino-bis-(3-ethylbenzothiazoline-6-sulfonicacid); AD: Alzheimer's disease; ALP: polysaccharide extracts isolated from Annona muricata leaves; ARE: antioxidant response element; DPPH: 1,1-diphenyl-picrylhydrazyl; DCFH-DA: 2ʹ,7ʹ-dichlorofluorescin diacetate; ECL: electrochemiluminescence; ERK: extracellular regulated kinase; FBS: Fetal bovine serum; FITC: fluorescein isothiocyanate; FRAP: ferric reducing antioxidant power; HO-1: Heme oxygenase-1; JNK: c-jun N-terminal kinase; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; MMP: mitochondrial membrane potential; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide; NQO1: NAD(P)H:quinine oxidoreductase 1, Nrf2: nuclear factor-E2-related factor 2; PD: parkinson's disease; PI3K: phosphatidylinositol-3kinase; PVDF: polyvinylidene difluoride; ROS: reactive oxygen species; SOD: Superoxidedismutase; TPTZ: tripydyltriazine Proposed mechanism of the neuroprotective activity induced by ALP in H 2 O 2 -treated HT22 hippocampus cells.