• Biomolecules & Therapeutics
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• 제22권3호
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• pp.246-253
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• 2014

Codonopsis lanceolata has been used as an herbal medicine for several lung inflammatory diseases, such as asthma, tonsillitis, and pharyngitis. Previously, we showed the neuroprotective effect of steamed and fermented C. lanceolata (SFC) in vitro and in vivo. In the current study, the treatment of HT22 cells with SFC decreased glutamate-induced cell death, suggesting that SFC protected HT22 cells from glutamate-induced cytotoxicity. Based on these, we sought to elucidate the mechanisms of the neuroprotective effect of SFC by measuring the oxidative stress parameters and the expression of Bax and caspase-3 in HT22 cells. SFC reduced contents of ROS, $Ca^{2+}$ and NO. Moreover, SFC restored contents of glutathione and glutathione reductase as well as inhibited Bax and caspase-3 activity in HT22 cells. These results indicate that steamed and fermented C. lanceolata (SFC) extract protected HT22 cells by anti-oxidative effect and inhibition of the expression of Bax and caspase-3.

• 생약학회지
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• 제45권2호
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• pp.161-167
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• 2014

Ganoderma lucidum L. (GL) is a traditional oriental medicine that has been widely used as anti-inflammatory, antitumor and anti-oxidant in Korea and other Asian countries. In this study, we investigated the ethanol extract of GL has neuroprotective effects in murine hippocampal HT22 cells. GL ethanol extract has the potent neuroprotective effects on glutamate-intoxicated cells by inducing the expression of heme oxygenase (HO)-1 in HT22 cells. GL ethanol extract increased JNK phosphorylation. Obviously, When we treated the GL extract with c-Jun N-terminal kinase (JNK) inhibitor (SP600125), HO-1 expression was reduced. Moreover, we found that GL treatment caused the nuclear accumulation of Nrf2. In conclusion, the ethanol extract of GL significantly protects glutamate-induced oxidative damage by induction of HO-1 via Nrf2, JNK pathway in mouse hippocampal HT22. These results suggest that GL ethanol extract would be a good source for taking active compounds and may be a potential pharmaceutical products for brain disorder induced by neuronal damage and oxidative stress.

• 약학회지
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• 제56권5호
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• pp.299-303
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• 2012

Homosyringaldehyde was isolated and identified from the 80% methanol extract of roots of Cynanchum paniculatum. C. paniculatum has been widely used for the treatment of various diseases such as neurasthenia, insomnia, dysmenorrheal and toothache. This compound exerted significant neuroprotective activities against glutamate-induced neurotoxicity in hippocampal HT22 cell line by 37.53% (at the concentration of $100{\mu}M$). We investigated mode of action of this compound. Homosyringaldehyde ($100{\mu}M$) significantly decreased the ROS level and $Ca^{2+}$ concentration in the oxidative stress induced HT22 cells by oxidative glutamate toxicity. Thus, our results suggest that homosyringaldehyde significantly protect HT22 cells against glutamate-induced oxidative stress, via antioxidative activities. As the results, we suggest that homosyringaldehyde may be useful in the treatment of neurogenerative disorders.

• 약학회지
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• 제47권2호
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• pp.85-92
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• 2003

Seok-jeong (SJ) is a solution of various metal ions and numerous other organic substances produced through extraction and fermentation of herbs and soil using geo-microbes, and it has been shown to improve symptoms of senile dementia. In this study, we investigated the protective effects of SJ against neurotoxicity of cadmium in HT22 hippocampal neuron cell line. SJ significantly protected from the cadmium-induced decreased cell viability measured by MTT assay (p＜0.01). The protective effects of SJ against cadmium toxicity were confirmed through observing morphological changes using inverted microscope. Additionally, SJ significantly repressed the formation of lipid peroxidation induced by high concentration of cadmium, and likewise, significantly repressed the reduction of glutathione by cadmium in HT22 cells. Vitamin C at the concentration found in SJ did not show any protective effect against cadmium toxicity in HT22 cells, indicating that vitamin C may not have a major role in the protective mechanism of SJ. Taken together, these results suggest that SJ may be a valuable agent for the protection of cadmium toxicity on the neuronal cells, and that the mechanism of the action of SJ may be due to reduced lipid peroxidation and increased glutathione level.

• 생약학회지
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• 제41권3호
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• pp.190-195
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• 2010

Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. NNMBS098, a composition comprising the water insoluble of the 70% EtOH extract of Zingiberis Rhizoma, showed the potent neuroprotective effects on glutamateinduced neurotoxicity by induced the expression of heme oxygenase (HO)-1 and increased HO activity in the mouse hippocampal HT22 cells. Furthermore, NNMBS098 caused the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) in mouse hippocampal HT22 cells. In addition, we found that treatment with c-Jun N-terminal kinase (JNK) inhibitor (SP600125) reduced NNMBS098-induced HO-1 expression and NNMBS098 also increased JNK phosphorylation. Therefore, these results suggest that NNMBS098 increases cellular resistance to glutamate-induced oxidative injury in mouse hippocampal HT22 cells, presumably through JNK pathway-Nrf2-dependent HO-1 expression.

• 생약학회지
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• 제42권2호
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• pp.175-181
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• 2011

Oxidative stress or accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate is one of the major excitatory neurotransmitter in the central nervous system (CNS). Glutamate contributes to fast synaptic transmission, neuronal plasticity, outgrowth and survival, behavior, learning and memory. In spite of these physiological functions, high concentration of glutamate causes neuronal cell damage, acute insults and chronic neuronal neurodegenerative diseases. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. NNMBS020, the water-insoluble fraction of the 70% EtOH extract of root barks of Dictamnus dasycarpus, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS020 makes the nuclear accumulation of Nrf2 and stimulates extracellular signal-regulated kinase (ERK) pathway. The ERK MAPK pathway inhibitor significantly reduced NNMBS020-induced HO-1 expression, whereas the JNK and p38 inhibitors did not. In conclusion, the water-insoluble fraction of the 70% EtOH extract of root barks of D. dasycarpus (NNMBS020) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 and ERK pathway in mouse hippocampal HT22 cells.

• 약학회지
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• 제55권4호
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• pp.314-318
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• 2011

Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. In the present study, we investigated the neuroprotective effects of the standard extracts of Taraxacum officinale Weber, one of the original plants of Taraxaci Herba, on glutamate-induced oxidative injury in mouse hippocampal HT22 cells. The standard EtOH extract of the aerial parts of T. officinale (NNMBS270) showed significant cytoprotective effects on glutamate-induced neurotoxicity and induced the expression of heme oxygenase (HO)-1 in the mouse hippocampal HT22 cells, while the roots' extract (NNMBS271) did not show neuroprotective effect. These results suggest that the extract of the aerial parts of T. officinale could be an effective candidate for the treatment of ROS-related neurological diseases.

• Natural Product Sciences
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• 제18권3호
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• pp.177-182
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• 2012

Oxidative stress potentially induces neurotoxicity which is believed to underlie several major age-related diseases of the central nervous system. This study sought to identify the cytoprotective effects of sixty-nine Cambodian plants against glutamate-induced cell death. Cultured HT22 cells were applied as an in vitro model, and neurotoxicity was induced in these neuronal cells by exposure to a determined concentration of glutamate. Sixty-nine plant sources, as Cambodia's indigenous species, were purchased from O'reusey Market, Phnom Penh, and extracted with ethanol. These extracts were screened for cytoprotective effects against glutamate-triggered neurotoxicity in HT22 cells at concentrations of 100 and 300 ${\mu}g/ml$. Of these, eight ethanol extracts, bark of Anacardium occidentale, bark and sapwood of Bauhinia pulla, flowers of Borassus flabellifer, stems and leaves of Coix lacryma-jobi, bark and sapwood of Diospyros nitida, sapwood of Dipterocarpus obtusifolius, stems of Oryza rufipogon, and fruits of Phyllanthus emblica, showed significant cytoprotective effects against glutamate-induced cell damage and degeneration in HT22 cells.

• Biomolecules & Therapeutics
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• 제20권3호
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• pp.306-312
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• 2012

Resveratrol (trans-3,5,4'-trihydroxystilbene) has received considerable attention recently for the potential neuroprotective effects in neurodegenerative disorders where heme oxygenase-1 (HO-1) and sirtuin 1 (SIRT1) represent promising therapeutic targets. Resveratrol has been known to increase HO-1 expression and SIRT1 activity. In this study, the effects of resveratrol and trans-3,5,4'-trimethoxystilbene (TMS), a resveratrol derivative, on cytotoxicity caused by glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation have been investigated by using murine hippocampal HT22 cells, which have been widely used as an in vitro model for investigating glutamate-induced neurotoxicity. Resveratrol protected HT22 neuronal cells from glutamate-induced cytotoxicity and increased HO-1 expression as well as SIRT1 activity in a concentration-dependent manner. Cytoprotection afforded by resveratrol was partially reversed by the specific inhibition of HO-1 expression by HO-1 small interfering RNA and the nonspecific blockage of HO-1 activity by tin protoporphyrin IX, but not by SIRT1 inhibitors. Surprisingly, TMS, a resveratrol derivative with methoxyl groups in lieu of the hydroxyl groups, and trans-stilbene, a non-hydroxylated analog, failed to protect HT22 cells from glutamate-induced cytotoxicity and to increase HO-1 expression and SIRT1 activity. Taken together, our findings suggest that the cytoprotective effect of resveratrol was at least in part associated with HO-1 expression but not with SIRT1 activation and, importantly, that the presence of hydroxyl groups on the benzene rings of resveratrol appears to be necessary for cytoprotection against glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation in HT22 neuronal cells.

• Natural Product Sciences
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• 제13권3호
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• pp.268-271
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• 2007

Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Bioassay-guided fractionation of the MeOH extract of the seeds of Alpinia katsumadai Hayata (Zingiberaceae) furnished three phenolic compounds, alpinetin (1), pinocembrin (2), and (+)-catechin (3). Compounds 2 and 3 showed the potent neuroprotective effects on glutamate-induced neurotoxicity and reactive oxygen species (ROS) generation in the mouse hippocampal HT22 cells. In addition, Compounds 2 and 3 showed significant DPPH free radical scavenging effect. These results suggest that compounds 2 and 3 could be the effective candidates for the treatment of ROS-related neurological diseases.