• Journal of the korean academy of Pediatric Dentistry
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• v.33 no.1
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• pp.13-24
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• 2006

Neuronal apoptotic events, consequently resulting in neuronal cell death, are occurred in hypoxic/ischemic condition. This cell death has been shown to be accompanied with the production of reactive oxygen species (ROS), which can attack cellular components such as nucleic acids, proteins and phospholipid. However, the underlying mechanisms of apoptosis induced in hypoxic/ischemic condition and its treatment methods are unsettled. Cobalt chloride $(CoCl_2)$ has been known to mimic hypoxic condition including the production of ROS. Epigallocatechin gallate (EGCG), a green tea polyphenol, has diverse pharmacologial activities in cell growth and death. This study was aimed to investigate the apoptotic mechanism by $CoCL_2$ and effects of EGCG on $CoCl_2-induced$ apoptosis in PC12 cells. Administration of $CoCl_2$ decreased cell survival in dose- and time-dependent manners and induced genomic DNA fragmentation. Treatment with $100{\mu}M$ EGCG for 30 min before PC12 cells were exposed to $150{\mu}M$ $CoCl_2$, being resulted in the cell viability and DNA fragmentation being rescued. $CoCl_2$ caused morphologic changes such as cell swelling and condensed nuclei whereas EGCG attenuated morphologic changes by $CoCl_2$. EGCG suppressed the apoptotic peak and a loss of ${\Delta}{\psi}_m$ induced by $CoCl_2$. $CoCl_2$ decreased Bcl-2 expression but Bax expression was not changed in $CoCl_2$- treated cells. EGCG attenuated the Bcl-2 underexpression by $CoCl_2$. $CoCl_2$ augumented the cytochrome c release from mitochondria into cytoplasm and increased caspase-8, -9 and caspase-3 activity a marker of the apoptotic executing stage. EGCG ameliorated the incruement in caspase-8, -9 and -3 activity, and cytochrome c release by $CoCl_2$ NAC (N-acetyl-cysteine), a scavenger of ROS, attenuated $CoCl_2-induced$ apoptosis in consistent with those of EGCG. These results suggest that $CoCl_2$ induces apoptotic cell death through both mitochondria- and death receptor-dependent pathway and EGCG has neuroprotective effects against $CoCl_2-induced$ apoptosis in PC12 cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1533-1543
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• 2016

The anti-stress effects of Punica granatum L. (family Lythraceae, PG) on $H_2O_2$/corticosterone (CORT)-induced stress in cells and sleep-deprived rats were investigated. The PG extract showed neuroprotective effects in SH-SY5Y cells against $H_2O_2$/CORT-induced stress. Sleep deprivation led to behavioral, hormonal, and biochemical alterations in the animal model. The effects of P. granatum on physiological, behavioral, and biochemical parameters aggravated by sleep deprivation were investigated. Sleep deprivation impaired physiological (survival, body weight, and drowsiness scores) and behavioral (rotarod, passive avoidance, hot hyperalgesia, and Y maze) parameters as well as biochemical factors (cortisol, serotonin, dopamine, testosterone, and growth factor I contents in serum). These parameters were significantly recovered by PG extract in a concentration-dependent manner. The PG extract also enhanced catalase, superoxide dismutase, and non-enzymatic antioxidative activities such as glutathione compared to sleep-deprived rats. On the basis of these results, our findings suggest that Punica granatum prevents impairment of body functions induced by sleep deprivation and related oxidative damage.

• Journal of Life Science
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• v.32 no.8
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• pp.601-610
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• 2022

P. tenebrifer (PT) belongs to the Diptera order and Stratiomyidae family. Recently, insect industry have been focused as food, animal feed and environmental advantages. γ-aminobutyric acid (GABA) and melatonin have been associated with regulating sleep and depression. GABA is the primary inhibitory neurotransmitter and is synthesized via biotransformation of monosodium glutamate (MSG) to GABA by lactic acid bacteria. In this study, we first used a GABA-enhanced PT extract, wherein GABA was enhanced by feeding MSG to PT. The underlying mechanisms preventing stress and insomnia were investigated in a corticosterone (CORT)-induced endoplasmic reticulum (ER) stress and chronic restraint stress (CRS)-exposed mouse model, as well as in pentobarbital (45 mg/kg)-induced sleep behaviors in mice. In the present study, the GABA peak was detected in high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) analysis and showed in Ptecticus tenebrifer water extract (PTW) but not in non-PTW extract. The results showed that PTW and Ptecticus tenebrifer with 70% ethanol extract (PTE) exerted neuroprotective effects by protecting against CORT-induced downregulation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP-response element binding protein (CREB) expression. In addition, PTW (300 mg/kg) significantly reduced CORT levels in CRS-exposed mice. Furthermore, PTW (100 and 300 mg/kg) significantly reduced sleep latency and increased total sleep duration in pentobarbital (45 mg/kg)-induced sleeping behaviors, which was related to serum melatonin levels. In conclusion, our results suggest that PTW exerts anti-stress and sleep-enhancing effects by regulating serum CORT and melatonin levels.

• Journal of Life Science
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• v.23 no.9
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• pp.1096-1103
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• 2013

Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.

• Korean Journal of Food Science and Technology
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• v.50 no.4
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• pp.383-390
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• 2018

Most neurodegenerative diseases are known to be influenced by oxidative stress. We investigated the anti-oxidative activity of the concentrate of fermented wild ginseng root culture (HLJG0701) containing ginsenosides Rg5 and Rk1. HLJG0701 showed effective DPPH and ABTS radical scavenging ability ($IC_{50}$: 16- and 4-fold dilution, respectively) and was inhibited dose-dependently by the $FeSO_4$-induced lipid peroxidation group (8- and 4-fold dilution: 2.3 and 1.5 nM, respectively). In MTT and LDH assays, 8-, 16-, 32- and 64-fold diluted HLJG0701 significantly increased cell viability by 70, 53, 35, and 26%, respectively. LDH released by HLJG0701 was reduced 1.3-fold with 8-fold diluted HLJG0701 compared to the $H_2O_2$-treated control. In addition, the inhibitory effect of HLJG0701 on oxidative stress in PC12 cells was confirmed by DCF-DA analysis (16-, 4-fold diluted HLJG0701: 50 and 68% ROS inhibition, respectively), TBARS (16- and 4-fold diluted HLJG0701: 50.7 and 46.5% inhibition, respectively), GPx (16- and 4-fold diluted HLJG0701: 133.3 and 227.3% release, respectively), and SOD analysis (16- and 4-fold diluted HLJG0701: 118.2 and 218.2% release, respectively). These results suggested that HLJG0701 protects neuronal cells by its anti-oxidative effects and hence can be a potential preventive material against neurodegenerative diseases.

• Journal of Life Science
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• v.21 no.5
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• pp.647-655
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• 2011

The neurotoxicity of aggregated amyloid ${\beta}$ ($A{\beta}$) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of apoptosis to neuron. Here, we investigated the neuroprotective effects of cilostazol, which acts as a phosphodiesterase III inhibitor, on $A{\beta}_{25-35}$-induced cytotoxicity in mouse neuronal cells and cognitive decline in the C57BL/6J AD mouse model via peroxisome proliferator-activated receptor (PPAR)-${\gamma}$ activation. $A{\beta}_{25-35}$ significantly reduced cell viability and increased the number of apoptotic-like cells. Cilostazol treatment recovered cells from $A{\beta}$-induced cell death as well as rosiglitazone, a PPAR-${\gamma}$ activator. These effects were suppressed by GW9662, an antagonist of PPAR-${\gamma}$ activity, indicative of a PPAR-${\gamma}$-mediated signaling. In addition, cilostazol and rosiglitazone also restored PPAR-${\gamma}$ activity levels that had been altered as a result of $A{\beta}_{25-35}$ treatment, which were antagonized by GW9662. Furthermore, cilostazol also markedly decreased the number of apoptotic-like cells and decreased the Bax/Bcl-2 ratio. Intracerebroventricular injection of $A{\beta}_{25-35}$ in C57BL/6J mice resulted in impaired cognitive function. Oral administration of cilostazol (20 mg/kg) for 2 weeks before $A{\beta}_{25-35}$ injection and once a day for 4 weeks post-surgery almost completely prevented the $A{\beta}_{25-35}$-induced cognitive deficits, as did rosiglitazone. Taken together, our findings suggest that cilostazol could attenuate $A{\beta}_{25-35}$-induced neuronal cell injury and apoptosis as well as promote the survival of neuronal cells, subsequently improving cognitive decline in AD, partly because of PPAR-${\gamma}$ activation. The phosphodiesterase III inhibitor cilostazol may be the basis of a novel strategy for the therapy of AD.

• Journal of Life Science
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• v.30 no.4
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• pp.331-342
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• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

• Journal of Life Science
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• v.20 no.3
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• pp.444-452
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• 2010

The purpose of this study was to investigate the effects of treadmill exercise on $A{\beta}$-42, cytochrome c, SOD-1, 2 and Sirt-3 protein expressions in brain cytosol and mitochondria in mutant (N141I) presenilin-2 transgenic mice with Alzheimer's disease (AD). The mice were divided into four groups (Non-Tg-sedentary, n=5; Non-Tg treadmill exercise, n=5; Tg-sedentary, n=5; Tg treadmill exercise, n=5). To evaluate the neuroprotective effect of treadmill exercise, Non-Tg and Tg mice were subjected to exercise training on a treadmill for 12 wk, after which their brain cytosol and mitochondria were evaluated to determine whether any changes in the cognitive performance, $A{\beta}$-42 protein, cytochrome c protein, anti-oxidant enzymes (SOD-1, SOD-2) and Sirt-3 protein had occurred. The results indicated that treadmill exercise resulted in amelioration in cognitive deficits of Tg mice. In addition, the expressions of mitochondrial $A{\beta}$-42 and cytosolic cytochrome c protein were decreased in the brains of Tg mice after treadmill exercise, whereas antioxidant enzymes, SOD-l and SOD-2 were significantly increased in response to treadmill exercise. Furthermore, treadmill exercise significantly increased the expression of Sirt-3 protein in Non-Tg and Tg mice. Taken together, these results suggest that treadmill exercise is a simple behavioral intervention which can sufficiently improve cognitive performance and inhibit $A{\beta}$-induced oxidative stress in AD.

• Journal of the Korean Applied Science and Technology
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• v.37 no.3
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• pp.448-462
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• 2020

Dietary nutrition is a critical lifestyle factor that can reduce the risk of future cognitive impairments caused by dementia. Accumulating evidence suggests that dietary supplementation with Sulforaphane may help the prevention of cognitive impairments and dementia. Thus, Sulforaphane-enriched broccoli extract would hold promise to improve cognitive impairments of dementia patients. Here, we have used broccoli extracts, prepared from broccoli cultivated in Magma Seawater, to test if the broccoli extracts can be dietary supplement to improve cognitive impairments. Magma Seawater originated from Jeju Island, Korea is unique in terms of containing high concentrations of usable minerals (Zinc, Vanadium and Germanium etc.). Broccoli, grown in Magma Seawater, would contain Sulforaphane and the extra amount of usable minerals. The chemical compositions of the broccoli extracts were analyzed using LC-Q-orbitrap to detect Sulforaphane and Glucoraphanin. Analysis method based on HPLC was developed for measurement of sulforaphane levels in the broccoli extracts. We have tested if the broccoli extracts have anti-apoptotic and anti-inflammatory effects on neuron-like SH-SY5Y cells. In addition, we examined if the broccoli extracts are able to upregulate expression of synaptic plasticity-associated proteins (BDNF and phospho-CREB) and to inhibit acetylcholine esterase (AchE) activity. We have shown that the broccoli extracts inhibited the apoptotic pathway and inflammatory responses. Finally, we present evidence showing that AchE activity was inhibited by the broccoli extracts, but expression of BDNF and phospho-CREB was upregulated. Taken together, these findings suggest that the broccoli extracts from Magma Seawater-grown broccoli would be a good source of dietary nutrition to improve cognitive impairments in the future.

• Korean Journal of Food Science and Technology
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• v.44 no.4
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• pp.428-433
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• 2012

Probiotics and their products, such as yogurt and cheese have been widely consumed in many countries with proven health benefits including anti-microbial activity and anti-diarrheal activity. LHFM (Lactobacillus helveticus - fermented milk) is a processed skim milk powder, fermented by a probiotics, L. helveticus IDCC3801. In the present study, we aimed to investigate the neuroprotective effects and the cognitive improvements of LHFM. LHFM itself did not show any cytotoxicity to the human neuroblastoma cell line, SH-SY5Y; however, it dose-dependently protected against glutamate-induced neuronal cell death. LHFM also attenuated scopolamine-induced memory deficit in Y-maze and Morris-water maze. In the analysis of hippocampus after a behavior test, LHFM significantly increased the acetylcholine level and also inhibited acetylcholine esterase activity. Therefore, the raised acetylcholine release partially contributes to the improvement of learning and memory by a treatment with LHFM. These results suggest that LHFM is an effective material for prevention or improvement of cognitive impairments caused by neuronal cell damage and central cholinergic dysfunction.