• Biomolecules & Therapeutics
• /
• v.19 no.3
• /
• pp.288-295
• /
• 2011

Amyloid beta ($A{\beta}$)-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD). In this study, we investigated the inhibitory effect of L-theanine, a component of green tea (Camellia sinensis) on $A{\beta}_{1-42}$-induced neurotoxicity and oxidative damages of macromolecules. L-theanine inhibited $A{\beta}_{1-42}$-induced generation of reactive oxygen species, and activation of extracellular signal-regulated kinase and p38 mitogenic activated protein kinase as well as the activity of nuclear factor kappa-B. L-theanine also signifi cantly reduced oxidative protein and lipid damage, and elevated glutathione level. Consistent with the reduced neurotoxic signals, L-theanine (10-50 ${\mu}g$/ml) concomitantly attenuated $A{\beta}_{1-42}$ (5 ${\mu}M$)-induced neurotoxicity in SK-N-MC and SK-N-SH human neuroblastoma cells. These data indicate that L-theanine on $A{\beta}$-induced neurotoxicity prevented oxidative damages of neuronal cells, and may be useful in the prevention and treatment of neurodegenerative disease like AD.

• Biomolecules & Therapeutics
• /
• v.25 no.5
• /
• pp.519-527
• /
• 2017

Excessive activation of microglia causes the continuous production of neurotoxic mediators, which further causes neuron degeneration. Therefore, inhibition of microglial activation is a possible target for the treatment of neurodegenerative disorders. Balanophonin, a natural neolignoid from Firmiana simplex, has been reported to have anti-inflammatory and anti-cancer effects. In this study, we aimed to evaluate the anti-neuroinflammatory effects and mechanism of balanophonin in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of balanophonin. The results indicated that balanophonin reduced not only the LPS-mediated TLR4 activation but also the production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), $Interleukin-1{\beta}$ ($IL-1{\beta}$), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), in BV2 cells. Balanophonin also inhibited LPS-induced inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) protein expression and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAPK. Interestingly, it also inhibited neuronal cell death resulting from LPS-activated microglia by regulating cleaved caspase-3 and poly ADP ribose polymerase (PARP) cleavage in N2a cells. In conclusion, our data indicated that balanophonin may delay the progression of neuronal cell death by inhibiting microglial activation.

• The Journal of Korea CHUNA Manual Medicine
• /
• v.2 no.1
• /
• pp.143-157
• /
• 2001

Objectives and Methods : To evaluate the mechanism of oxidative damage by xanthine oxydase(XO) and hypoxanthine(HX)-induced oxygen radicals, MTT assay and NR assay were carried out after the cultured mouse spinal sensory neurons were preincubated for 4 hours with various concentrations of XO/HX. And the amount of total protein. neurofilament EIA. lipid peroxidation and LDH activity were measured, to evaluate the protective effect of Herbar Chelidonii(HC) water extract on cultured spinal sensory neurons damaged by XO/HX. after the cultured mouse spinal sensory neurons were preincubated with various concentrations of HC water extract for 3 hours prior to exposure of XO/HX. Results : XO/HX decreased significantly the survival rate of the cultured mouse sensory neurons by NR assay and MTT assay In proportion to concentration and exposed time. In proportion to concentration and exposed time on cultured spinal sensory neurons, XO/HX showed the quantitative decrease of neurofilament by EIA. the decrease of total protein amount by SRB assay and the Increase of lipid peroxidation as well as LDH. HC showed the quantitative increase of neurofilament and total protein, but showed the decrease of lipid peroxidation and LDH activity against the neurotoxicity of XO/HX. Conclusions : From the above results, it is concluded that XO/HX have a neurotoxic effect on cultured spinal sensory neurons and that the herbs extract, such as HC, prevent the toxicity of XO/HX effectively in that they decrease lipid peroxidation and LDH activity.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.2
• /
• pp.374-379
• /
• 2003

To evaluate the mechanism of oxidative damage by Xanthine oxidase(XO) and hypoxanthine(HX)-induced oxygen radicals, XTT assay was carried out. Neurofilament EIA and PKC activity were measured to evaluate the protective effect of Jingansikpung-tang(JST) and Gamijingansikpung-tang(GJST) water extract on cultured spinal sensory neurons damaged by XO/HX, after the cultured mouse spinal sensory neurons were preincubated with various concentrations of JST and GJST water extract for 3 hours prior to exposure of XO/HX. The results were XO/HX decreased significantly, in proportion to concentration and exposed time, the survival rate of the cultured mouse sensory neurons on XTT assay. And in proportion to concentration and exposed time on cultured spinal sensory neurons, XO/HX showed the quantitative decrease of neurofilament by EIA, increase of PKC activity, but JST and GJST showed the neuroprotective effects against decrease of neurofilament and increase of PKC activity by XO/HX. From the above results, it is concluded that XO/HX have a neurotoxic effect on cultured spinal sensory neurons and the herbs water extract, such as JST and GJST prevent the toxicity of XO/HX effectively.

• Biomolecules & Therapeutics
• /
• v.11 no.4
• /
• pp.214-223
• /
• 2003

Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) have become popular recreational drugs of abuse in many countries. Although the neurotoxic damage caused by METH and MDMA is characterized by degeneration of the dopaminergic and serotonergic systems in brain, the molecular and cellular mechanisms remain to be clarified. Therefore, the purposes of this study were to confirm the capability of METH and MDMA to induce apoptosis and to clarify the action of its molecular mechanism by using serotonergic JAR cells and dopaminergic SK-N-SH cells. METH and MDMA were dose-dependently cytotoxic to human serotonergic JAR cells and dopaminergic SK-N-SH cells. The morphological change of apoptosis was found in Giemsa staining and TUNEL and further verified in DNA fragmentation analysis. Immunoblotting analysis revealed proteolytic cleavage of caspase-3 and -9 and change of bcl-2 and bax proteins. These results suggest that METH and MDMA may induce caspase-dependent apoptosis via the mitochondrial cell death pathway and METH and MDMA-induced neurotoxicity may happen to broadly and independently of both dopaminergic and serotonergic systems.

• BMB Reports
• /
• v.42 no.7
• /
• pp.444-449
• /
• 2009

Different neurodegenerative disorders like prion disease, is caused by protein misfolding conformers. Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic. To investigate the possible mechanism of neurotoxicity due to accumulation of PrP in cytosol, a PrP mutant lacking the signal and GPI (CytoPrP) was introduced into the SH-SY5Y cell. MTT and trypan blue assays indicated that the viability of cells expressing CytoPrP was remarkably reduced after treatment of MG-132. Obvious apoptosis phenomena were detected in the cells accumulated with CytoPrP, including loss of mitochondrial transmembrane potential, increase of caspase-3 activity, more annexin V/PI-double positive-stained cells and reduced Bcl-2 level. Moreover, DNA fragmentation and TUNEL assays also revealed clear evidences of late apoptosis in the cells accumulated CytoPrP. These data suggest that the accumulation of CytoPrP in cytoplasm may trigger cell apoptosis, in which mitochondrial relative apoptosis pathway seems to play critical role.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.6
• /
• pp.1500-1508
• /
• 2003

This study was performed to clarify the neurotoxic mechanism of nerve cells damage by brain ischemia. The cytotoxic effect of ischemia was determined by XTT assay, NR assay, superoxide dismutase(SOD) activity, amount of malondialdehyde(MDA), lactate dehydrogenase(LDH) activity, protein synthesis and tumor necrosis factor(TNF)-α activities after cerebral neurons derived from mouse were exposed to ischemia for 1∼30 minutes. In addition, the protective effect of extract of Daejo-whan(DJW) on ischemia-induced neurotoxicity was examined in these cultures. 1. Ischemia decreased cell number and viability by XTT assay or NR assay when cultured cerebral neurons were exposed to 95% N2/5% CO₂ for 1∼20 minutes in these cultures. 2. Ischemia decreased SOD and protein syntheses, but it increased amount of MDA and, LDH and TNF-α activities in these cultures. 3. In the neuroprotective effect of DJW extracts on cerebral neurons damaged by ischemia, DJW extracts increased SOD activity and protein synthesis. While, it decreased amount of MDA and, LDH and TNF-α activities after cerebral neurons preincubated with herb extracts. It suggests that brain ischemia has neurotoxicity on cultured mouse cerebral neurons, and the herb extract such as DJW was very effective in blocking the neurotoxicity induced by ischemia in cultured mouse cerebral neurons.

• Korean Journal of Biological Psychiatry
• /
• v.11 no.2
• /
• pp.94-103
• /
• 2004

Objective:There have been a kind of transmethylation theory that high homocysteine serum concentration affects schizophrenia by neurotoxic mechanism and clinical reports that some schizophrenic patients with high homocysteine were improved by high folate ingestion. This study was done to confirm previous research results and find the clinical characteristics of schizophrenia showing high serum homocysteine and low folate. Method:We compared the serum levels of homocysteine, folate and vitamin B12 level between 234 schizophrenic patients(male 99, female 135) group and 234 normal controls(male 99, female 135) group. The subjects of two groups were age and sex matched. The evaluated clinical characteristics items were sex, age, onset of disease, hereditary loading, disease course, hallucination and subtype of schizophrenia. Results:1) Homocysteine level of the schizophrenia group was significantly higher than the normal control group and folate level of the schizophrenia group was significantly lower than the normal control group. Homocysteine level was more negatively correlated with folate level in the schizophrenia group than the normal control group. 2) The percentage of high homocysteine(above 12.46umol/L;90 percentile of normal control) was 33.8% of schizophrenia patients and 51.5% of male schizophrenia. The percentage of low folate(below 3.8nM/L;bottom tertile of normal control) was 66.2% of schizophrenia. 3) In low folate group and not-low folate group, schizophrenia showed significantly higher homocysteine level than normal control. Especially, low folate schizophrenia group showed significantly higher homocysteine level than low folate normal control group. Conclusions:Some schizophrenia patients with high serum homocysteine may be genetic defector and having low folate serum level. In that case, folate ingestion could be a good management for clinical improvement.

• Korean Journal of Psychosomatic Medicine
• /
• v.30 no.2
• /
• pp.73-79
• /
• 2022

Objectives : Suicide is a global social problem. Social burden caused by suicide is gradually increasing. Various efforts have been made to prevent suicide. Lifestyle changes to western style, especially diet changes, have increased the risk for suicide. Therefore, in this study, we discussed diet as an adjuvant treatment for suicide. Methods : In this review, we summarized the biochemical mechanism of suicide, and diet as a risk factor for suicide and diet as a protective factor through a web search. Results : In this study, biochemical mechanisms for suicide were reviewed and diet as a risk factor and diet as a protective factor for suicide were investigated. It was confirmed that neurotoxic effects such as oxidative stress and inflammation in the neural system could increase the risk of suicide. Based on results of previous studies on the relationship between suicide and diet, it was found that heavy use of alcohol, coffee, carbonated soft drink, and fast food were risk factors for suicide. Protective factors for suicide included antioxidants such as vitamin C, carotene, and anti-inflammatory agents such as omega-3 fatty acids found in seafood in large amounts. Conclusions : The only treatment for suicide is prevention. In this context, effectiveness, accessibility, and safety are important for preventing for suicide. Antioxidants and anti-inflammatory agents that are relatively safe and readily available to the public could be effective adjuvant treatments to decrease the risk of suicide. In addition, it is necessary to educate the public on reducing diets that could increase the risk of suicide