• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.171-180
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• 2021

Caffeine, a methylxanthine analog of purine bases, is a compound that is largely consumed in beverages and medications for psychoactive and diuretic effects and plays many beneficial roles in neuronal stimulation and enhancement of anti-tumor immune responses by blocking adenosine receptors in higher organisms. In single-cell eukaryotes, however, caffeine somehow impairs cellular fitness by compromising cell wall integrity, inhibiting target of rapamycin (TOR) signaling and growth, and overriding cell cycle arrest caused by DNA damage. Among its multiple inhibitory targets, caffeine specifically interacts with phosphatidylinositol 3-kinase (PI3K)-related kinases causing radiosensitization and cytotoxicity via specialized intermediate molecules. Caffeine potentiates the lethality of cells in conjunction with several other stressors such as oxidants, irradiation, and various toxic compounds through largely unknown mechanisms. In this review, recent findings on caffeine effects and cellular detoxification schemes are highlighted and discussed with an emphasis on the inhibitory interactions between caffeine and its multiple targets in eukaryotic microorganisms such as budding and fission yeasts.

• Food Science and Biotechnology
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• 제17권2호
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• pp.343-348
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• 2008

In this study, antioxidant activity of methanol extract of Glycyrrhiza uralensis Fisch (GUE) against $H_2O_2$-induced DNA damage in human leucocytcs and cell death in PC12 cells was determined. The effect of GUE on $H_2O_2$-induced DNA damage in human leucocytcs was evaluated by the comet assay, where GUE ($1-50\;{\mu}g/mL$) was a dose dependent inhibitor of DNA damage induced by $H_2O_2$. The protective effect of GUE against $H_2O_2$-induced damage on PC12 cells was investigated by MTT reduction assay and lactate dehydrogenase release assay. A marked reduction in cell survival induced by $H_2O_2$ was significantly prevented by $1-50\;{\mu}g/mL$ of GUE. The enzyme activity of caspase-3 was elevated in $H_2O_2$-treated PC12 cells, while preincubation with GUE for 30 min inhibited $H_2O_2$-induced caspase-3 activation in a dose-dependent manner. In conclusion, GUE ameliorates $H_2O_2$-induced DNA damage in human leucocytes and has neuroprotective effect by preventing cell death in PC12 cell, suggesting that GU may be a potential candidate for novel therapeutic agents for neuronal diseases associated with oxidative stress.

• Journal of Korean Neurosurgical Society
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• 제29권8호
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• pp.1008-1018
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• 2000

Objective : Glutamate induced excitotoxicity is one of the leading causes of cell death under pathologic condition. However, there is controversy whether excitotoxicity may also participate in the neuronal death under low intensity insult such as simple hypoxia or hypoglycemia. To investigate the role of NMDA receptor in low intensity insult, we chose anoxia as the method of injury and used organotypically cultured hippocampal slice as the material of experiment. Materials & Methods : The hippocampal slices cultured for 2-3 weeks were exposed to 60 minutes of complete oxygen deprivation(anoxia). Neuronal death was assessed with Sytox stain. Corrected optical density of fluorescence in gray scale, used as cellular death indicator, was obtained from pictures taken at 24 and 48 hours following the insult. The well-known in vivo phenomenon of regional difference in susceptibility of hippocampal sub-fields to ischemic insult was reproduced in HOSC(hippocampal organotypic slice culture) by complete oxygen deprivation injury. Results : $CA_1$ was the most vulnerable to complete oxygen deprivation in hippocampus while $CA_3$ was resistant. Oxygen deprivation for 10 and 20 minutes with glucose(6.5g/l) present was insufficient to induce neuronal death in the cultured hippocampal slice. However, after 30 minutes exposure under anoxic condition, neuronal death was able to be detected in the center of $CA_1$ area. The intensity and area of fluorescence indicating cell death correlated with the duration of oxygen deprivation. NMDA receptor and non-NMDA receptor blocking with MK-801(30 & $60{\mu}M$) and CNQX($100{\mu}M$) did not provide cellular protection to HOSC against damage induced by oxygen deprivation, but increased intracellular calcium buffering capacity with BAPTA-AM($10{\mu}M$) was effective in preventing neuronal death (p=0.01, Student's t-test). Cycloheximide($1{\mu}g/ml$, $10{\mu}g/ml$) provided no protection to HOSC against insult of complete oxygen deprivation for 60 minutes and combined therapy of MK-801(30 & $60{\mu}M$) and cycloheximide(1 & $10{\mu}g/ml$) was also ineffective in preventing neuronal death. Conclusion : The results of this study show that the another mechanism not associated with glutamate receptor(NMDA & non NMDA) may play major role in cell death mechanisms induced by complete oxygen deprivation and increased intracellular calcium during anoxia may participate in the neuronal death mechanism of oxygen deprivation. Further investigation of the calcium entry channel activated during oxygen deprivation is necessary to understand the neuronal death of anoxia.

• 한국약용작물학회지
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• 제13권2호
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• pp.95-102
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• 2005

Caulis Bambusae in Taenia is widely used in Korea and China due to its various pharmacological activity. The present study aims to investigate the effect of the methanol extract of Caulis Bambusae in Taenia (CB) from Phyllostachys nigra Munro var. henonis Stapf (Gramineae) on amyloid ${\beta}$ protein (25-35) $(A{\beta}\;(25-35))$, a synthetic 25-35 amyloid peptide, -induced neurotoxicity using cultured rat cortical neurons. CB, over a concentration range of $10-50{\mu}g/{\mu}l$, inhibited the $A{\beta}\;(25-35)\;(10\;{\mu}M)$-induced neuronal cell death, as assessed by a 3-[4,5-dimethyIthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. CB $(50\;{\mu}g/{\mu}l)$ inhibited glutamate release into medium induced by $10\;{\mu}M\;A{\beta}$, (25-35) which was measured by HPLC. Pretreatment of CB $(50\;{\mu}g/{\mu}l)$ inhibited $10{\mu}M\;A{\beta}$ (25-35)-induced elevation of cytosolic calcium concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, fluo-4 AM, and generation of reactive oxygen species. These results suggest that CB prevents $A{\beta}$ (25-35)-induced neuronal ell damage in vitro.

• Journal of Applied Biological Chemistry
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• 제63권4호
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• pp.357-363
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• 2020

Oxidative stress caused by the overproduction of reactive oxygen species (ROS) is known as an etiology of neurodegenerative diseases. Populus tomentiglandulosa (PT), a member of the Salicaceae family, is widely grown in Korea and has been reported to exert protective effects on cerebral ischemia by attenuating of oxidative stress and neuronal damage. In the present study, we investigated the antioxidant activity and neuroprotective effects of an ethanol extract and four fractions [n-butanol, ethyl acetate (EtOAc), chloroform, and n-hexane] of PT under in vitro and cellular systems. The extract and four fractions of PT showed 1,1-diphenyl-2-picrylhydrazyl (DPPH), •OH, and O2- radical scavenging activities in a dose-dependent manner. In particular, the EtOAc fraction of PT had the strongest DPPH, •OH, and O2- radical scavenging activities among the extract and other fractions. Therefore, we further investigated the neuroprotective effect of the EtOAc fraction of PT against oxidative stress in H2O2-induced SH-SY5Y cells. Treatment with H2O2 significantly decreased cell viability and lactate dehydrogenase (LDH) release, and it also increased the ROS levels compared to the normal group. However, treatment with the EtOAc fraction of PT significantly increased cell viability. Moreover, the EtOAc fraction of PT-treated group significantly suppressed ROS production and LDH release compared to the H2O2-induced control group. In conclusion, our findings indicated that PT had in vitro antioxidant activity and neuroprotective effects against oxidative stress. Therefore, PT could be used as a natural agent for protection against oxidative stress.

• 대한본초학회지
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• 제22권1호
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• pp.7-12
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• 2007

Objectives : In Alzheimer's disease(AD), free radical oxidative stress caused by amyloid beta-peptide may lead to DNA damage, neuronal dysfunction, neurotoxicity and cell death, Hwangryunhaedok-tang(HHT) is traditionally used for the treatment of pyrogenetic diseases. To develop a new anti-AD drug from natural herb, HHT was selected and extracted in this study. Methods : The antioxidant activities of HHT water extract powder were examined by hydroxyl radical-induced DNA strand nicking assay, and antioxidative enzymes expression assay in H4IIE cell. In addition, HHT was examined for the inhibitory effect on the acetylcholinesterase(AChE) using by Ellman's coupled assay. Results: The HHT exhibit DNA protective effect in the hydroxyl radical-induced DNA Strand nicking assay, mRNA expression of superoxide dismutase and glutathione peroxidase were recovered at a normal level by HHT treatment in H4IIE cell. Furthermore, water extract of HHT showed inhibitory effect on AChE activity. Conclusion : These results suggest that HHT may be effective in delaying and preventing AD progression related to the free radical-induced DNA damage and AChE activity.

• 생약학회지
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• 제52권3호
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• pp.149-156
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• 2021

Excessive glutamate can cause oxidative stress in neuronal cells and this can be the reason for neurodegenerative disease. In this study, we investigated the protective effect of Spirulina maxima hot ethanol extract on mouse hippocampal HT22 cell of which glutamate receptor has no function. HT22 cells were pre-treated with S. maxima sample at a dose dependent manner (1, 10 and 100 ㎍/ml). After an hour, glutamate was treated. Cell viability, reactive oxygen species (ROS) accumulation, Ca²⁺ influx, decrease of mitochondrial membrane potential level and glutathione related assays were followed by then. S. maxima ethanol extract improved the cell viability by suppressing the ROS and Ca²⁺ formation, retaining the mitochondrial membrane potential level and protecting the activity of the antioxidant enzymes compared with group of vehicle-treated controls. These suggest that S. maxima may decelerate the neurodegeneration by attenuating neuronal damage and oxidative stress.

• 생약학회지
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• 제46권2호
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• pp.109-115
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• 2015

This study was investigated the radical scavenging effect and the protective activity of caffeic acid (CA) against oxidative stress. CA showed strong 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and hydroxyl radical ( OH) scavenging activity, showing 42.00% and 87.22% at 5 μM concentration of DPPH and ·OH scavenging activity, respectively. Furthermore, we studied protective activity of CA from amyloid beta (A${\beta}$_25-35) and lipopolysaccharide (LPS) induced neuronal cell damage and neuronal inflammation using C6 glial cells. The treatment of A${\beta}$_25-35 to C6 glial cell showed declines in cell viability and high generation levels of reactive oxygen species (ROS). However, the treatment of CA increased cell viability. The treatment of 5 ${{\mu}M}$ CA led to the elevation of cell viability from 59.28% to 81.22%. In addition, the production of ROS decreased cellular levels of ROS by the treatment of CA. The treatment of LPS to C6 glial cells increased significant elevation of nitric oxide (NO) production, while CA decreased NO production significantly. The production of NO increased by the treatment of LPS to 131.08%, while CA at the concentration of 1 ${{\mu}M}$ declined the NO production to 104.86%. The present study indicated thatCA attenuated A${\beta}$_25-35-induced neuronal oxidative stress and inflammation by LPS, suggesting as a promising agent for the neurodegenerative diseases.

• 한국미생물·생명공학회지
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• 제49권2호
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• pp.138-147
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• 2021

The overproduction of reactive nitrogen species (RNS) and reactive oxygen species (ROS) causes oxidative damage to neuronal cells, leading to the progression of neurodegenerative diseases. In this study, we determined the nitric oxide radical (NO), hydroxyl radical (·OH), and superoxide anion radical (O₂^-) scavenging activities of apigenin. Our results showed that apigenin exhibited remarkable, concentration-dependent ·OH, O₂^-, and NO radical scavenging activities. Particularly, apigenin indicated the strongest ·OH radical scavenging activity with 93.38% in the concentration of 100 µM. Furthermore, we also investigated the protective effects of apigenin against hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y cells. The H₂O₂ treatment resulted in a significant decrease in cell viability, as well as an increase in lactate dehydrogenase (LDH) release and ROS production compared with the H₂O₂-nontreated SH-SY5Y cells. However, the cell viability significantly increased in the apigenin-treated group, as well as inhibited ROS generation and LDH release compared with the H₂O₂-induced control group. To elucidate the protective mechanisms of apigenin against oxidative stress in SH-SY5Y, we analyzed the apoptosis-related protein expression. The apigenin treatment resulted in the downregulated expression of apoptosis-related protein markers, such as cytochrome C, cleaved caspase-3, poly (ADP)-ribose polymerase (PARP), and B-cell lymphoma 2-associated X (Bax), as well as the upregulated expression of anti-apoptosis markers such as B-cell lymphoma 2 (Bcl-2). In this study, we report that apigenin exhibits a neuroprotective effect against oxidative stress in SH-SY5Y cells. These results suggest that apigenin may be considered as a potential agent for neurodegenerative disease prevention.

• 농업생명과학연구
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• 제44권2호
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• pp.57-66
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• 2010

자색고구마 추출물의 항산화 효과와 산화적 스트레스로 유도된 PC12 신경세포에 대한 보호효과에 대하여 연구하였다. 자색고구마 추출물의 총 페놀함량은 44.25 mg/g, monomeric anthocyanin 함량은 2,394 mg/L로 나타났다. 자색고구마 추출물의 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylben-zthiazoline-6-sulfonic acid) (ABTS) radical 소거활성, ferric reducing/antioxidant power (FRAP) 및 환원력은 농도 의존적으로 항산화 활성이 증가하였다. MTT {3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazoliumbromide} reduction assay를 이용하여 자색고구마 추출물의 신경세포 보호효과를 측정한 결과, 세포 생존율이 두드러지게 증가하는 것으로 나타났다. 산화적 스트레스는 신경세포막 손상 정도를 증가시키기 때문에 lactate dehydrogenase (LDH) release assay와 neutral red uptake assay를 이용하여 세포막 손상 보호효과를 조사한 결과 자색고구마 추출물 처리구는 대조구에 비하여 산화적 스트레스로 유도된 세포막 손상 보호효과가 농도 의존적으로 나타났다. 따라서 자색고구마 추출물은 천연 항산화 소재 및 알츠하이머성 치매와 같은 신경퇴행성 질환의 예방 소재로서의 활용 가능성이 기대된다.