• 제목/요약/키워드: Nrf2 activation

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LPS로 유도된 RAW264.7 대식세포에 대한 헛개나무(Hovenia dulcis) 추출물의 항염증 효과 (Anti-inflammatory Activity of Extracts of Hovenia dulcis on Lipopolysaccharides-stimulated RAW264.7 Cells)

  • 우현심;이선민;허정두;이민성;김영수;김대욱
    • 한국자원식물학회지
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    • 제31권5호
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    • pp.466-477
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    • 2018
  • 본 연구는 헛개나무 잎, 줄기, 뿌리로부터 얻어진 메탄올 추출물의 항염증 효과를 구명하기 위해서 수행되었다. LPS로 염증이 유도된 RAW264.7 세포 내 부위별 추출물을 동시에 처리하여 염증 매개성 물질인 NO 생성량 분석 결과 $40{\mu}g/m{\ell}$농도에서 뿌리(94.7%)와 줄기(42.6%)에서는 효과가 있는 반면 잎에서는 효과가 없는 것으로 확인되었다. 이 중 탁월한 효과를 보인 뿌리 추출물(RE)의 항염증 효과 및 관련 분자적 기전을 확인하였다. 그 결과, 염증 반응의 주요 경로인 NF-kB 및 MAPK 신호전달경로에서 RE가 LPS로 유도된 NF-kB의 핵 이동을 억제하고, ERK, JNK, p38의 인산화를 억제함으로써 iNOS, COX-2의 발현이 감소되고, NO와 pro-inflammatory cytokine (IL-6, $IL-1{\beta}$, $TNF-{\alpha}$)의 생성이 억제됨을 확인하였다. 또한 RE는 대식세포에서 Nrf2를 활성화시켜 항염증성 단백질인 HO-1 발현을 유도하여 항염증 효과를 나타내었다. 또한, RE로부터 주요 성분을 분리한 후 NMR과 MS 기기를 이용하여 구조 동정된 27-O-protocatechuoylbetulinic acid 화합물에서도 높은 항염증 효과를 확인하였다. 이러한 연구결과는 헛개나무뿌리와 그 주요성분은 의약품 소재 및 기능성 식품 등의 기능성 소재로 활용될 수 있는 기초적인 정보를 제공할 것으로 생각된다.

Protodioscin protects porcine oocytes against H2O2-induced oxidative stress during in vitro maturation

  • So-Hee Kim;Seung-Eun Lee;Jae-Wook Yoon;Hyo-Jin Park;Seung-Hwan Oh;Do-Geon Lee;Da-Bin Pyeon;Eun-Young Kim;Se-Pill Park
    • Animal Bioscience
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    • 제36권5호
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    • pp.710-719
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    • 2023
  • Objective: The present study investigated whether protodioscin (PD), a steroidal saponin mainly found in rhizome of Dioscorea species, alleviates oxidative stress-induced damage of porcine oocytes during in vitro maturation. Methods: Oocytes were treated with different concentrations of PD (0, 1, 10, 100, and 200 µM) in the presence of 200 µM H2O2 during in vitro maturation. Following maturation, spindle morphology and mitogen-activated protein kinase activity was assessed along with reactive oxygen species level, GSH activity, and mRNA expression of endogenous antioxidant genes at the MII stage. On the day 7 after parthenogenetic activation, blastocyst formation rate was calculated and the quality of embryo and mRNA expression of development-related genes was evaluated. Results: Developmental competence was significantly poorer in the 0 µM PD-treated (control) group than in the non-treated (normal) and 10 µM PD-treated (10PD) groups. Although the reactive oxygen species level did not significantly differ between these three groups, the glutathione level and mRNA expression of antioxidant genes (superoxide dismutase 1 [SOD1], SOD2, nuclear factor erythroid 2-related factor 2 [Nrf2], and hemo oxygenase-1 [HO-1]) were significantly higher in the normal and 10PD groups than in the control group. In addition, the percentage of oocytes with defective spindle and abnormal chromosomal alignment was significantly lower and the ratio of phosphorylated p44/42 to total p44/42 was significantly higher in the normal and 10PD groups than in the control group. The total cell number per blastocyst was significantly higher in the 10PD group than in the control group. The percentage of apoptotic cells in blastocysts was highest in the control group; however, the difference was not significant. mRNA expression of development-related genes (POU domain, class 5, transcription factor 1 [POU5F1], caudal type homeobox 2 [CDX2], Nanog homeobox [NANOG]) was consistently increased by addition of PD. Conclusion: The PD effectively improves the developmental competence and quality of blastocysts by protecting porcine oocytes against oxidative stress.

어류병원성 세균 및 C2C12 근원세포에 대한 polyamine 계열 물질인 spermidine의 항균 및 항산화 활성 (Antibacterial and Antioxidant Activity of Spermidine, a Natural Polyamine, on Fish Pathogenic Bacteria and C2C12 Myoblast Cells)

  • 황보현;최은옥;김민영;지선영;홍수현;박철;차희재;김석만;김희수;황혜진;최영현
    • 한국해양바이오학회지
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    • 제11권2호
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    • pp.42-51
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    • 2019
  • We compared the antibacterial activities of spermidine and astaxanthin against two gram-positive bacteria such as Streptococcus parauberis and S. iniae to find new antibacterial candidates. We also evaluated the preventive effects of spermidine against oxidative stress-induced cytotoxicity in C2C12 myoblasts. Our results indicated that spermidine has more significant antibacterial activities than astaxanthin against both two fish pathogenic bacteria as well as gram-negative bacteria Escherichia coli used as a control group. Minimum inhibitory concentration and minimum bactericidal concentration of spermidine were 0.25 mM and 1 mM against S. parauberis, 1 mM and 3 mM against S. iniae, and 0.5 mM and 1.5 mM against E. coli, respectively. In addition, the postantibiotic effect lasted from 7 h, 5 h and 6 h for S. parauberis, S. iniae and E. coli, respectively. The results also showed that the decreased C2C12 cell viability by H2O2 could be attributed to the induction of DNA damage and apoptosis accompanied by the increased production of reactive oxygen species, which was remarkably protected by spermidine. Additionally, the antioxidant effect of spermidine was associated with the activation of Nrf2 signaling pathway. According to the data, spermidine may be a potential lead compound which can be further optimized to discover novel antibacterial and antioxidant agents.

Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes

  • Kim, Yoon Hee;Jung, Jae In;Jeon, Young Eun;Kim, So Mi;Oh, Tae Kyu;Lee, Jaesun;Moon, Joo Myung;Kim, Tae Young;Kim, Eun Ji
    • Nutrition Research and Practice
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    • 제16권1호
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    • pp.14-32
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    • 2022
  • BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells. MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2. CONCLUSIONS: The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

엉겅퀴 70% 에탄올 추출물의 RAW264.7 세포에서 Heme oxygenase-1 발현을 통한 항염증 효과 (Anti-inflammatory Effect of the Cirsium japonicum var. ussuriense 70% Ethanolic Extract in RAW264.7 Cells by Heme oxygenase-1 Expression)

  • 이동성;김경수;리빈;최현규;케오썸엘;전기용;박준형;김윤철
    • 생약학회지
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    • 제43권1호
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    • pp.39-45
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    • 2012
  • Cirsium japonicum var. ussuriense has long been used in herbal medicine for the treatment of arthritis, dyspepsia, and bleeding in Korea. In the present study, we investigated anti-inflammatory effects of C. japonicum var. ussuriense against lipopolysaccharide(LPS)-induced activation in RAW264.7 cells by the expression of heme oxygenase (HO)-1. The 70% EtOH extract of the aerial parts of C. japonicum var. ussuriense (CJE), showed the potent anti-inflammatory effects on LPS-induced inflammation in RAW264.7 cells. The anti-inflammatory effect of CJE was demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2). Furthermore CJE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increased HO activity in RAW264.7 macrophages. The effects of CJE on LPS-induced NO and $PGE_2$ productions were partially reversed by an HO-1 inhibitor, tin protoporphyrin (SnPP). Therefore, it is suggested that CJE-induced HO-1 expression plays a role of the resulting anti-inflammatory effects in macrophages. These results suggest that CJE may be a promising candidate for the treatment of inflammatory diseases.

당지질로 유도한 염증반응에서 Piceatannol의 항염증 기전 연구 (Mechanism Underlying the Anti-Inflammatory Action of Piceatannol Induced by Lipopolysaccharide)

  • 조한진;심재훈;소홍섭;윤정한
    • 한국식품영양과학회지
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    • 제41권9호
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    • pp.1226-1234
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    • 2012
  • 본 연구에서는 염증반응을 조절하는 다양한 신호전달체계를 중심으로 분자생물학적 방법을 통해 piceatannol의 항염증 기전을 규명하였다. LPS로 염증반응을 유도한 Raw 264.7 대식세포에서 piceatannol은 iNOS의 발현 억제를 통해 NO의 생성을 감소시키고 염증성 사이토카인(TNF-${\alpha}$, IL-6, IL-$1{\beta}$)의 생성을 감소시켰다. 염증반응을 조절하는 신호전달체계 중 piceatannol은 LPS에 의해 유도된 $I{\kappa}B$의 분해와 p65의 핵으로의 이동을 억제하고, LPS에 의해 유도된 SAPK/JNK의 인산화를 억제하였다. 또한 piceatannol은 LPS와 IL-6(LPS에 의해 증가됨)에 의한 STAT3의 활성화를 억제하였다. 뿐만 아니라 piceatannol은 Nrf2의 핵 내 축적을 야기하고 ARE의 transcriptional activity를 증가시켜 HO-1의 발현을 증가시켰다. 본 연구의 결과, piceatannol은 NF-${\kappa}B$와 AP-1, STAT3 신호전달의 억제를 통해, 그리고 HO-1의 발현 증가를 통해 항염증 효과를 나타내었다(Fig. 8).