• 제목/요약/키워드: nrf-2

검색결과 453건 처리시간 0.03초

Korean red ginseng water extract produces antidepressant-like effects through involving monoamines and brain-derived neurotrophic factor in rats

  • Tzu-wen Chou ;Huai-Syuan Huang;Suraphan Panyod ;Yun-Ju Huang ;Lee-Yan Sheen
    • Journal of Ginseng Research
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    • 제47권4호
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    • pp.552-560
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    • 2023
  • Background: Ginseng Radix (Panax ginseng Meyer, Araliaceae) has been used medicinally to treat the brain and nervous system problems worldwide. Recent studies have revealed physiological effects that could potentially benefit cognitive performance or mood. The present study aimed to investigate the antidepressant effects of Korean red ginseng water extract (KGE) and its active component in an unpredictable chronic mild stress (UCMS)-induced animal model and elucidate the underlying mechanisms. Methods: The antidepressant potential of the UCMS model was evaluated using the sucrose preference test and open field tests. The behavioral findings were further corroborated by the assessment of neurotransmitters and their metabolites from the prefrontal cortex and hippocampus of rats. Three doses of KGE (50, 100, and 200 mg/kg) were orally administered during the experiment. Furthermore, the mechanism underlying the antidepressant-like action of KGE was examined by measuring the levels of brain-derived neurotrophic factor (BDNF)/CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) proteins in the prefrontal cortex of UCMS-exposed rats. Results: KGE treatment normalized UCMS-induced depression-related behaviors. Neurotransmitter studies conducted after completing behavioral experiments demonstrated that KGE caused a reduction in the ratio of serotonin and dopamine, indicating a decrease in serotonin and dopamine turnover. Moreover, the expression of BDNF, Nrf2, Keap1 and AKT were markedly increased by KGE in the prefrontal cortex of depressed rats. Conclusion: Our results provide evidence that KGE and its constituents exert antidepressant effects that mediate the dopaminergic and serotonergic systems and expression of BDNF protein in an animal model.

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis

  • Hasan Dirik;Ahmet Sevki Taskiran;Ziad Joha
    • The Korean Journal of Pain
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    • 제37권3호
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    • pp.233-246
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    • 2024
  • Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

자외선 B를 조사한 인간유래각질세포에서 두릅순 에탄올추출물의 산화적 스트레스 억제효과 (Suppressive effects of ethanol extract of Aralia elata on UVB-induced oxidative stress in human keratinocytes)

  • 곽충실;양지원
    • Journal of Nutrition and Health
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    • 제49권3호
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    • pp.135-143
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    • 2016
  • 두릅순에서 얻은 70% 에탄올 추출물의 in vitro 항산화 효과를 측정하고, UVB에 의한 피부광노화를 유도하는 주요 원인인 ROS의 생성을 억제하는 효과가 있는지 알아보기 위하여 인간유래각질세포 (HaCaT)를 이용하여 실험을 수행하였다. 두릅순의 총 폴리페놀과 플라보노이드 함량은 각각 20.15 mg tannic acid/g dry wt, 18.75 mg rutin/g dry wt 이었고, 70% 에탄올 추출물의 DPPH 라디칼을 소거능 ($IC_{50}$)은 $98.5{\mu}g\;AA\;eq./mL$이었으며, $1,000{\mu}g/mL$ 농도에서 ABTS 라디칼 소거능과 환원력 (FRAP)은 각각 $41.8{\mu}g\;ascorbic\;acid\;(AA)\;eq./mL$$29.7{\mu}g\;AA\;eq./mL$로 우수한 항산화효과를 보였다. 두릅순 추출물을 HaCaT 세포에 24시간 전처리했을 때 UVB 조사에 의한 ROS 생성이 유의하게 감소되었으며, 산화적 스트레스에 민감하게 반응하는 전사인자인 Nrf-2와 각질세포에서 ROS를 제거하는 역할을 하는 주요 항산화효소인 SOD-1의 단백질 수준의 발현은 증가한 반면, UVB 조사에 의하여 증가하였던 HO-1의 단백질 발현은 감소되었다. 그러나, catalase의 단백질 발현에는 영향을 주지 못하였다. 본 연구결과는 두릅순 70% 에탄올 추출물에 함유된 항산화효능이 우수한 어떤 페놀화합물들이 UVB 조사로 인하여 생성된 ROS를 직접적으로 제거할 뿐 아니라 각질세포에 존재하는 방어시스템의 활성화를 통하여 산화적 스트레스로 인한 악영향을 막아줄 가능성을 제시하고 있다. 따라서, 두릅순 70% 에탄올 추출물은 UVB에 의한 피부손상 및 피부광노화를 억제하는 기능성식품 및 화장품 소재로 이용될 수 있을 것이다.

THE ESSENTIAL ROLE OF PI3-KINASE IN THE INDUCTION OF GLUTATHIONE S-TRANSFERASE BY TERT-BUTYLHYDROQUINONE AND OLTIPRAZ: DIFFERENTIAL EFFECTS ON Nrf2/ARE ACTIVATION

  • Kim, Sang-Geon;Kang, Keon-Wook
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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    • pp.96-106
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    • 2001
  • The phase II detoxifying enzymes are inducible by a variety of compounds and play an essential role for the protection of cells. Many of chemoprotective agents trigger cellular signals for the phase II enzyme induction, which subsequently activate gene transcription through ARE activation.(omitted)

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HepG2 cell에서 quercetin의 HO-1 발현을 통한 mitochondria의 생합성 유도 효과에 관한 연구 (Quercetin Induces Mitochondrial Biogenesis via HO-1 Expression in HepG2 Cell)

  • 강재구;장상철;이기승;김진희;정명수
    • 대한한의정보학회지
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    • 제21권1호
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    • pp.14-22
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    • 2015
  • Flavonoids show diverse bioactivities, such as anti-oxidant, anti-cancer, anti-allergic, anti-inflammatory, and anti-viral. Quercetin is one of the flavonoids present in a wide range of plants, especially onions and consumed all over the world. Recently, it is known that quercetin induces mitochondrial biogenesis in vivo and in vitro. However, detail mechanism of these actions remains unknown. We investigated quercetin's effects on mitochondrial biogenesis in HepG2 cells, and determined the mechanisms involved. We found that quercetin treatment induced the expression of mitochondrial biogenesis activators, $PGC-1{\alpha}$, NRF-1, TFAM, and mitochondrial proteins, cytochorome c and complex IV (COXIV). Moreover, amount of mitochondrial DNA was also increased by quercetin. Quercetin has been known to induce heme oxygenase (HO)-1 in several types of cells. Here, we found quercetin induces HO-1, and inhibition of HO-1 or CO, which is product of HO-1, decreased quercetin-induced mitochondrial biogenesis such as induction of $PGC-1{\alpha}$, NRF-1, TFAM, cytochorome c, COXIV, and mitochondrial DNA. These findings imply that quercetin can increase mitochondrial biogenesis via HO-1/CO system. High glucose results in dysfunction of mitochondria biogenesis. In the present study, 25 mM glucose decreased mitochondrial biogenesis and this damage was restored by quercetin. Conversely, inhibition of HO-1 or CO inhibited quercetin-induced mitochondrial biogenesis rescue. These results suggest that quercetin enhances mitochondrial biogenesis via HO-1/CO system and hence, can rescue mitochondria from damage by high glucose.

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Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Mitochondrial DNA Replication and PGC-1α Gene Expression in C2C12 Muscle Cells

  • Lee, Mak-Soon;Shin, Yoonjin;Moon, Sohee;Kim, Seunghae;Kim, Yangha
    • Preventive Nutrition and Food Science
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    • 제21권4호
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    • pp.317-322
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    • 2016
  • Mitochondrial biogenesis is a complex process requiring coordinated expression of nuclear and mitochondrial genomes. The peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-$1{\alpha}$) is a key regulator of mitochondrial biogenesis, and it controls mitochondrial DNA (mtDNA) replication within diverse tissues, including muscle tissue. The aim of this study was to investigate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mtDNA copy number and PGC-$1{\alpha}$ promoter activity in $C_2C_{12}$ muscle cells. mtDNA copy number and mRNA levels of genes related to mitochondrial biogenesis such as PGC-$1{\alpha}$, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam) were assayed by quantitative real-time PCR. The PGC-$1{\alpha}$ promoter from -970 to +412 bp was subcloned into the pGL3-basic vector, which includes a luciferase reporter gene. Both EPA and DHA significantly increased mtDNA copy number, dose and time dependently, and up-regulated mRNA levels of PGC-$1{\alpha}$, NRF1, and Tfam. Furthermore, EPA and DHA stimulated PGC-$1{\alpha}$ promoter activity in a dose-dependent manner. These results suggest that EPA and DHA may modulate mitochondrial biogenesis, which was partially associated with increased mtDNA replication and PGC-$1{\alpha}$ gene expression in $C_2C_{12}$ muscle cells.

Harmal Extract Induces Apoptosis of HCT116 Human Colon Cancer Cells, Mediated by Inhibition of Nuclear Factor-κB and Activator Protein-1 Signaling Pathways and Induction of Cytoprotective Genes

  • Elkady, Ayman I;Hussein, Rania A;El-Assouli, Sufian M
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.1947-1959
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    • 2016
  • Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the second most common type of cancer worldwide in both men and women. It accounts yearly for approximately 9% of all new cases of cancers. Furthermore, the current chemotherapeutic regimens seem unsatisfactory, so that exploration of novel therapeutic modalities is needed. The present study was undertaken to investigate the inhibitory effects of a crude alkaloid extract (CAERS) of a medicinal herb, Rhazya stricta, on proliferation of CRC HCT116 cells and to elucidate mechanisms of action. To achieve these aims, we utilized MTT, comet, DNA laddering and gene reporter assays, along with Western blot and RT-PCR analyses. Results: We found that CAERS inhibited cell proliferation and induced apoptotic cell death in HCT116 cells. Hallmarks of morphological and biochemical signs of apoptosis were clearly evident. CAERS down-regulated DNA-binding and transcriptional activities of NF-${\kappa}B$ and AP-1 proteins, while up-regulating expression of the Nrf-2 protein. It also down-regulated expression levels of the ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin and VEGF and up-regulated levels of Bax, caspase-3/7 and -9, p53, p21, Nrf-2. Markedly, it promoted mRNA expression levels of cytoprotective genes including the hemeoxygenase-1, NAD(P)H quinine oxidoreductase 1 and UDP-glucuronyltransferase. Conclusions: These findings indicate that CAERS exerts antiproliferative action on CRC cells through induction of apoptotic mechanisms, and suggest CAERS could be a promising agent for studying and developing novel chemotherapeutic agents aimed at novel molecular targets for the treatment of CRC.

R&D평가센터의 건축계획특성에 관한 연구 (A Study on the Architectural Plan Characteristics of R&D Evaluation Center)

  • 임양빈
    • 한국산학기술학회논문지
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    • 제20권12호
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    • pp.816-821
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    • 2019
  • 본 논문은 연구지원의 중추역할을 수행하고 있는 R&D 평가센터의 기능과 역할에 대한 수요가 증가하고 있는 가운데, 효율적이고 효과적인 연구지원을 위해서는 평가센터의 물리적 공간에 대한 건축적인 평가와 처방을 다루고 있다. 이를 위해서 각 분야의 국내 연구자들을 대상으로 설문조사를 실시하였고, 도출된 결과를 토대로 주차공간 부족은 지하 1,2층 주차장을 설치하여 주차난을 해소하고, 지상층에는 컨벤션센터, 통합전산센터, 심사평가장, 심사대기실, 휴게실, 심사평가위원휴게실을 설치하여 R&D연구정보·평가를 위한 공간을 확보함으로써, R&D연구정보·평가의 기능에 맞는 공간을 제시하고 있다. 구체적으로 3~5층은 중소형심사평가장, 대기실, 휴게실, 2층은 화상심사평가장, 심사평가장, 대기실, 교류 및 소통의 장, 휴게실, 1층은 컨벤션센터, 소회의실, 통합전산센터, 지하1층은 주차장과 계획서 및 보고서 접수창고, 지하2층은 기계전기실, 주차장으로 구성하였다. 한편 본 연구의 목적은 R&D평가센터의 공간과 시설에 대한 사용자 관점의 진단을 통해 문제점 및 수요를 도출하고, 가상공간을 활용하여 연구정보 관리와 학술연구 평가에 최적화된 R&D평가센터 신축의 기본계획을 수립한 후, 해당 시설의 건축적 타당성을 검증하는데 있다.