• 제목/요약/키워드: MAPKs/$NF-{\kappa}B$ pathway

검색결과 45건 처리시간 0.024초

Anti-inflammatory Effects of Abeliophyllum distichum Flower Extract and Associated MAPKs and NF-κB Pathway in Raw264.7 Cells

  • Lee, Jin-Wook;Kang, Yoon-Joong
    • Korean Journal of Plant Resources
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    • 제31권3호
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    • pp.202-210
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    • 2018
  • Abeliophyllum distichum is a medicinal plant used in regional traditional medicine to relieve pain in inflammatory processes. In this study, anti-inflammatory effects of Abeliophyllum distichum flower (ADF) extract were examined. Furthermore, possible molecular mechanisms of the anti-inflammatory effects were dissected. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced pro-inflammatory cytokine production in murine macrophage-like cell line Raw264.7 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK, and MAPK, and the nuclear expression of nuclear factor NF-${\kappa}B$ p65 were investigated by Western blot analysis. The extract of ADF significantly decreased the production of pro-inflammatory cytokines. In addition, the extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-${\kappa}B$ p65 in activated cells. Our findings provide evidence for the popular use of Abeliophylli distichum in inflammation around Goesan region and also suggest that the flower extract has potential therapeutic benefits against various inflammatory diseases.

Luteolin and luteolin-7-O-glucoside inhibit lipopolysaccharide-induced inflammatory responses through modulation of NF-${\kappa}B$/AP-1/PI3K-Akt signaling cascades in RAW 264.7 cells

  • Park, Chung Mu;Song, Young-Sun
    • Nutrition Research and Practice
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    • 제7권6호
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    • pp.423-429
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    • 2013
  • Luteolin is a flavonoid found in abundance in celery, green pepper, and dandelions. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-inflammatory capacity of luteolin and one of its glycosidic forms, luteolin-7-O-glucoside, were compared and their molecular mechanisms of action were analyzed. In lipopolysaccharide (LPS)-activated RAW 264.7 cells, luteolin more potently inhibited the production of nitric oxide (NO) and prostaglandin E2 as well as the expression of their corresponding enzymes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) than luteolin-7-O-glucoside. The molecular mechanisms underlying these effects were investigated to determine whether the inflammatory response was related to the transcription factors, nuclear factor (NF)-${\kappa}B$ and activator protein (AP)-1, or their upstream signaling molecules, mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K). Luteolin attenuated the activation of both transcription factors, NF-${\kappa}B$ and AP-1, while luteolin-7-O-glucoside only impeded NF-${\kappa}B$ activation. However, both flavonoids inhibited Akt phosphorylation in a dose-dependent manner. Consequently, luteolin more potently ameliorated LPS-induced inflammation than luteolin-7-O-glucoside, which might be attributed to the differentially activated NF-${\kappa}B$/AP-1/PI3K-Akt pathway in RAW 264.7 cells.

Anti-inflammatory Activities of Ethanol Extracts of Dried Lettuce (Lactuca sativa L.) (건조 상추 에탄올 추출물의 항염증 활성)

  • Lee, Eun-Joo;Seo, Yu-Mi;Kim, Yong-Hyun;Chung, Chungwook;Sung, Hwa-Jung;Sohn, Ho-Yong;Park, Jong-Yi;Kim, Jong-Sik
    • Journal of Life Science
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    • 제29권3호
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    • pp.325-331
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    • 2019
  • Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including $IL-1{\alpha}$, $IL-1{\beta}$, IL-1F6, $TNF-{\alpha}$, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of $NF-{\kappa}B$ p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and $NF-{\kappa}B$ pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, $NF-{\kappa}B$, and Nrf2/HO-1 pathways.

Anti-inflammatory effects of proanthocyanidin-rich red rice extract via suppression of MAPK, AP-1 and NF-κB pathways in Raw 264.7 macrophages

  • Limtrakul, Pornngarm;Yodkeeree, Supachai;Pitchakarn, Pornsiri;Punfa, Wanisa
    • Nutrition Research and Practice
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    • 제10권3호
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    • pp.251-258
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    • 2016
  • BACKGROUND/OBJECTIVES: Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS: Pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B ($NF-{\kappa}B$), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS: Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-${\alpha}$, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and $NF-{\kappa}B$ transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced $NF-{\kappa}B$ and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION: These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, $NF-{\kappa}B$, and MAPKs pathways.

Inhibitory Effect of Semen Sinapis Albae on Immediate Hypersensitivity Reaction (백개자의 즉시형 과민 반응에 대한 억제 효과)

  • Lee, Kyou-Young;Hong, Chul-Hee
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • 제27권4호
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    • pp.177-188
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    • 2014
  • 목적 : 본 연구에서는 백개자 열수추출물이 활성화된 대식세포 및 사람 비만세포주, HMC-1에서 염증 반응을 효과적으로 억제하는가를 관찰하고자 하였다. 방법 : 대식세포에 여러 농도의 백개자 열수추출물을 가한 뒤 LPS로 염증을 유도하여 NO 생산, iNOS와 COX-2 단백질 발현을 관찰하였으며 HMC-1에도 여러 농도의 백개자 열수추출물을 가한 후 PMACI로 염증을 유도하여 histamine 분비와 NF-${\kappa}B$ 활성 및 $I{\kappa}B$-${\alpha}$의 인산화, MAPKs pathway에 대한 저해효과를 관찰하였다. 결과 : 백개자 열수추출물은 대식세포에서 LPS로 유도된 NO 생성 및 INOS, COX-2 단백질 발현을 농도 의존적으로 저해하였으며 HMC-1에서 PMACI로 유도된 histamine의 분비와 p38 MAPK, ERK, JNK의 인산화 반응 및 $I{\kappa}B$-${\alpha}$의 인산화와 NF-${\kappa}B$의 활성을 저해하였다. 결론 : 백개자 열수추출물은 대식세포 및 비만세포의 활성을 저해함으로써 알레르기 질환의 치료에 사용될 잠재성이 크다고 사료된다.

RANK Signaling Pathways and Key Molecules Inducing Osteoclast Differentiation

  • Lee, Na Kyung
    • Biomedical Science Letters
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    • 제23권4호
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    • pp.295-302
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    • 2017
  • Mononuclear osteoclast precursors derived from hematopoietic progenitors fuse together and then become multinucleated mature osteoclasts by macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL). Especially, the binding of RANKL to its receptor RANK provides key signals for osteoclast differentiation and bone-resorbing function. RANK transduces intracellular signals by recruiting adaptor molecules such as TNFR-associated factors (TRAFs), which then activate mitogen activated protein kinases (MAPKs), Src/PI3K/Akt pathway, nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and finally amplify NFATc1 activation for the transcription and activation of osteoclast marker genes. This review will briefly describe RANKL-RANK signaling pathways and key molecules critical for osteoclast differentiation.

Anti-inflammatory Effects of Belamcanda Chinensis Water Extract (사간 물 추출물의 항염증 효과)

  • Park, Sung-Joo;Kim, Soo-Kon
    • Journal of Physiology & Pathology in Korean Medicine
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    • 제24권3호
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    • pp.410-415
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    • 2010
  • The purpose of this study was to investigate the anti-inflammatory effects of aqueous extract from Belamcanda chinensis (BC) on the RAW 264.7 cells. To evaluate the anti-inflammatory effects of BC, we examined the cytokine productions including nitric oxide (NO), interleukin (IL)-1b, IL-6 and tumor necrosis factor-a (TNF-a) in lipopolysaccharide (LPS)-induced RAW 264.7 cells and also inhibitory mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kB) using Western blot. BC inhibited LPS-induced production of NO, IL-6 and TNF-a but not of IL-1b in RAW 264.7 cells. BC respectively inhibited the activation of MAPKs such as c-Jun NH2-terminal kinase (JNK) and p38 but not of extracelluar signal-regulated kinase (ERK 1/2) and NF-kB in the LPS-stimulated RAW 264.7 cells. Taken together, Our results showed that BC down-regulated LPS-induced NO, IL-6 and TNF-a productions mainly through JNK and p38 MAPK pathway.

Effect of Atractylodis Rhizoma Alba on Osteoclast Formation (백출의 파골세포 분화에 미치는 영향)

  • Park, Sung-Tae;Lee, Myeung-Su;Jeon, Byung-Hun;Park, Kie-In;Oh, Jae-Min
    • Journal of Physiology & Pathology in Korean Medicine
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    • 제25권1호
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    • pp.109-114
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    • 2011
  • Atractylodis Rhizoma Alba is commonly used herbal medicine and it has been known that has immuno-regualtory effects and anti-cancer effects. The inhibition of osteoclastogenesis is essential for the prevention and treatment of osteoporosis. The aim of this study was to evaluate the effects of Atractylodis Rhizoma Alba on osteoclast differentiation in vitro and on resorbing activity of osteoclast. Osteoclast formation was evaluated in bone marrow cells (BMC) in the presence or absence of Atractylodis Rhizoma Alba. The expression of c-fos, tartrate-resistant acid phosphatase (TRAP), OSCAR, DC-STAMP, cathepsin K, MafB and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of TNF receptor-associated factor-6 (TRAF-6), c-fos and NFATc1 protein were assessed by Western blot analysis. Also the correlation with MAPKs and NF-${\kappa}B$ pathways were measured by using Western blot analysis. With bone resorption study, I tried to evaluate the inhibitory effects of Atractylodis Rhizoma Alba on mature osteoclast function. Atractylodis Rhizoma Alba inhibited the RANKL induced osteoclastic differentiation from bone marrow macrophage in a dose dependant manner without cellular toxicity. Gene expression of c-fos and NFATc1 was significantly down regulated with Atractylodis Rhizoma Alba treatment. Atractylodis Rhizoma Alba markedly inhibited the RANKL-induced osteoclastogenesis through suppression of nuclear factor kappa b (NF-${\kappa}B$) pathway, down stream pathway of p38, ERK and JNK pathway. Taken together, I concluded that Atractylodis Rhizoma Alba have beneficial effect on osteoporosis by inhibition of osteoclast differentiation and by inhibition of functioning osteoclast. Thus I expect that Atractylodis Rhizoma Alba could be a treatment option for osteoporosis.

Anti-Inflammatory Effect of Chondrus nipponicus Yendo Ethanol Extract on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells (LPS로 유도된 RAW 264.7 세포에 대한 가락진두발 에탄올 추출물의 항염증 효과)

  • Kim, Min-Ji;Bae, Nan-Yong;Kim, Koth-Bong-Woo-Ri;Park, Ji-Hye;Park, Sun-Hee;Jang, Mi-Ran;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • 제45권2호
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    • pp.194-201
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    • 2016
  • The anti-inflammatory activity of ethanol extract from Chondrus nipponicus Yendo (CNYEE) was investigated by measuring production of a lipopolysaccharide-induced inflammatory response mediator. CNYEE had no cytotoxic effects on proliferation of macrophages compared to the control. CNYEE significantly inhibited (over 50%) NO production at $50{\mu}g/mL$, with inhibitory effects on expression levels of cytokines such as interleukin (IL)-6, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and IL-$1{\beta}$. In particular, IL-6 inhibitory activity of CNYEE was higher than 70% at $100{\mu}g/mL$. CNYEE also reduced protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor (NF)-${\kappa}B$ in a dose-dependent manner. CNYEE also significantly reduced phosphorylation of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Therefore, these results suggest that CNYEE may have anti-inflammatory effects by modulating the NF-${\kappa}B$ and mitogen-activated protein kinases signaling pathways and may be used as an anti-inflammatory therapeutic material.

Luteolin 5-O-glucoside from Korean Milk Thistle, Cirsium maackii, Exhibits Anti-Inflammatory Activity via Activation of the Nrf2/HO-1 Pathway

  • Jung, Hyun Ah;Roy, Anupom;Abdul, Qudeer Ahmed;Kim, Hyeung Rak;Park, Hee Juhn;Choi, Jae Sue
    • Natural Product Sciences
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    • 제23권3호
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    • pp.183-191
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    • 2017
  • Luteolin 5-O-glucoside is the major flavonoid from Korean thistle, Cirsium maackii. We previously reported the anti-inflammatory activities of luteolin 5-O-glucoside in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In this study, we determined the anti-inflammatory mechanisms of luteolin 5-O-glucoside through the inhibition of nitric oxide (NO) production in vitro and in vivo. Results revealed that luteolin 5-O-glucoside dose-dependently inhibited NO production and expression of iNOS and COX-2 in LPS-induced RAW 264.7 cells. Luteolin 5-O-glucoside also significantly inhibited the translocation of $NF-{\kappa}B$, the activation of MAPKs, and ROS generation in LPS-induced RAW 264.7 cells. In addition, protein expressions of Nrf-2 and HO-1 were also upregulated by luteolin 5-O-glucoside treatment. Moreover, luteolin 5-O-glucoside inhibited ${\lambda}-carrageenan-induced$ mouse paw edema by 65.34% and 48.31% at doses of 50 and 100 mg/kg body weight, respectively. These findings indicate potential anti-inflammatory effect of luteolin 5-O-glucoside particularly by downregulating $NF-{\kappa}B$ and upregulating HO-1/Nrf-2 pathway.