Neuroprotective effect of polysaccharide separated from Perilla frutescens Britton var. acuta Kudo against H2O2-induced oxidative stress in HT22 hippocampus cells

Abstract

This study was carried out to evaluate the neuroprotective activity of polysaccharide extracts isolated from Perilla frutescens (PEPF) in H₂O₂-treated HT22 hippocampus cells. The PEPF treatment was found to increase the anti-oxidant activities of HT22 hippocampus cells. PEPF treatment resulted in a significant protection of HT22 hippocampus cells against H₂O₂-induced neurotoxicity, this protection ultimately occurred through an inhibition of ROS-mediated intracellular Ca²⁺ levels leading to MAPKs and NF-κB, as well as the accumulation of PI3K/AKT and Nrf2-mediated HO-1/NQO1 pathways. Furthermore, PEPF not only decreased the expression of Bax, cytochrome c, and cleaved caspases-3, -8, and -9, but also increased the expression of PARP and Bcl-2 in the H₂O₂-treated HT22 hippocampus cells, which overall contributed to the neuroprotective action. PEPF retains its mitochondrial membrane potential and reduces the elevated levels of sub-G1 phase and apoptotic morphological features induced by H₂O₂. It also reduces the malondialdehyde levels and enhances the intracellular SOD activity.

Keywords: ABTS2: 2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonicacid); AD: Alzheimer’s disease; ARE: antioxidant response element; DCFH-DA: 2′,7′-dichlorofluorescin diacetate; DPPH: 1,1-diphenyl-picrylhydrazyl; 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; PEPF: polysaccharide extracts isolated from Perilla frutescens; PI3K: phosphatidylinositol-3kinase; PVDF: polyvinylidene difluoride; Perilla frutescens Britton var. acuta Kudo; ROS: reactive oxygen species; SOD: Superoxidedismutase; TPTZ: tripydyltriazine; neuroprotection; neurotoxicity; oxidative stress; polysaccharide.