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Endoplasmic reticulum (ER) stress-related unfolded peptide accumulation is closely associated with the development of neurodegenerative diseases known as protein misfolding disorders. The antioxidative properties of kimchi, a traditional Korean fermented vegetable dish, have been well established. In this study, the neuroprotective effects of the kimchi methanol extract (KME) were examined in high-cholesterol diet (HCD)-fed mice. The animals were fed a HCD, with oral administration of either KME (KME group, 200 mg·kg bw -1 ·day -1 , n = 10) or distilled water (Control group, n = 10) for 8 weeks. Compared with the levels in the control group, the reactive oxygen species, peroxynitrite, and lipid peroxidation levels in the brain were significantly decreased in the KME group (P < .05), whereas the glutathione level was increased (P < .05). In addition, the ER stress biomarkers, phospho-eukaryotic initiation factor 2 subunit α, glucose-regulated protein 78, X-box binding protein 1, inositol-requiring enzyme 1, and C/EBP homologous protein and the nuclear factor-kappaB-mediated inflammation were significantly reduced in the KME group (P < .05). In contrast, the expression levels of antioxidative enzymes regulated by nuclear factor erythroid 2-related factor-2 were elevated (P < .05). The amyloid-beta expression levels of the KME group were lower than that of the control group (P < .05). Moreover, the expression levels of Bcl-2-associated X, and caspases-3 and -9 were downregulated, with a concomitant upregulation of B cell lymphoma 2 (P < .05). Accordingly, KME provide neuronal cell protection via suppressing ER stress and caspase cascade signaling.

Numerous studies have suggested that neuronal cells are protected against oxidative stress-induced cell damage by antioxidants, such as polyphenolic compounds. Phellinus linteus (PL) has traditionally been used to treat various symptoms in East Asian countries. In the present study, we prepared an ethyl acetate extract from the fruiting bodies of PL (PLEA) using hot water extraction, ethanol precipitation, and ethyl acetate extraction. The PLEA contained polyphenols as its major chemical component, and thus, we predicted that it may exhibit antioxidant and neuroprotective effects against oxidative stress. The results showed that the pretreatment of human brain neuroblastoma SK-N-MC cells with the PLEA (0.1-5 μg/mL) significantly and dose-dependently reduced the cytotoxicity of H2O2 and the intracellular ROS levels and enhanced the expression of HO-1 (heme oxygenase-1) and antioxidant enzymes, such as CAT (catalase), GPx-1 (glutathione peroxidase-1), and SOD-1 and -2 (superoxide dismutase-1 and -2). The PLEA also directly scavenged free radicals. PLEA pretreatment also significantly attenuated DNA fragmentation and suppressed the mRNA expression and activation of mitogen-activated protein kinases extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 kinase, which are induced by oxidative stress and lead to cell death. PLEA pretreatment inhibited the activation of the apoptosis-related proteins caspase-3 and poly (ADP-ribose) polymerase. These results demonstrate that the PLEA has neuroprotective effects against oxidative stress (H2O2)-induced neuronal cell death via its antioxidant and anti-apoptotic properties. PLEA should be investigated in an in vivo model on its potential to prevent or ameliorate neurodegenerative disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)