• Title/Summary/Keyword: MAPK signaling pathways

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Protective Effects of the Ethanol Extract of Viola tianshanica Maxim against Acute Lung Injury Induced by Lipopolysaccharides in Mice

  • Wang, Xue;Yang, Qiao-Li;Shi, Yu-Zhu;Hou, Bi-Yu;Yang, Sheng-Qian;Huang, Hua;Zhang, Li;Du, Guan-Hua
    • Journal of Microbiology and Biotechnology
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    • v.27 no.9
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    • pp.1628-1638
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    • 2017
  • Viola tianshanica Maxim, belonging to the Violaceae plant family, is traditionally used in Uighur medicine for treating pneumonia, headache, and fever. There is, however, a lack of basic understanding of its pharmacological activities. This study was designed to observe the effects of the ethanol extract (TSM) from Viola tianshanica Maxim on the inflammation response in acute lung injury (ALI) induced by LPS and the possible underlying mechanisms. We found that TSM (200 and 500 mg/kg) significantly decreased inflammatory cytokine production and the number of inflammatory cells, including macrophages and neutrophils, in bronchoalveolar lavage fluid. TSM also markedly inhibited the lung wet-to-dry ratio and alleviated pathological changes in lung tissues. In vitro, after TSM ($12.5-100{\mu}g/ml$) treatment to RAW 264.7 cells for 1 h, LPS ($1{\mu}g/ml$) was added and the cells were further incubated for 24 h. TSM dose-dependently inhibited the levels of proinflammatory cytokines, such as NO, $PGE_2$, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$, and remarkably decreased the protein and mRNA expression of $TNF-{\alpha}$ and IL-6 in LPS-stimulated RAW 264.7 cells. TSM also suppressed protein expression of $p-I{\kappa}Ba$ and p-ERK1/2 and blocked nuclear translocation of $NF-{\kappa}B$ p65. The results indicate that TSM exerts anti-inflammatory effects related with inhibition on $NF-{\kappa}B$ and MAPK (p-ERK1/2) signaling pathways. In conclusion, our data demonstrate that TSM might be a potential agent for the treatment of ALI.

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

  • Yeo, Eun Ji;Eum, Won Sik;Yeo, Hyeon Ji;Choi, Yeon Joo;Sohn, Eun Jeong;Kwon, Hyun Jung;Kim, Dae Won;Kim, Duk-Soo;Cho, Sung-Woo;Park, Jinseu;Han, Kyu Hyung;Lee, Keun Wook;Park, Jong Kook;Shin, Min Jea;Choi, Soo Young
    • Biomolecules & Therapeutics
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    • v.29 no.3
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    • pp.321-330
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    • 2021
  • Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

In vitro Anti-oxidative and Anti-inflammatory Activities of Horse-bone Extract via Up-regulation of Heme-oxygenase 1 (말뼈추출물의 Hemeoxygenase-1의 발현 조절을 통한 시험관내 항염증 효과)

  • Im, Eun Ju;Lee, Ki-Ja;Cho, Gil-Jae;Kim, Hyun-Kyoung;Kim, Suk;Rhee, Man Hee
    • Journal of agriculture & life science
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    • v.50 no.2
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    • pp.139-150
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    • 2016
  • Few studies have been reported that horse-bone extract(HBE) can prevent and treatment of bone diseases. However, HBE' therapeutic activities are still not fully understood. This study determined whether HBE up-regulates hemeoxygenase 1(HO-1) and this mediates its anti-inflammatory effect in murine macrophages.Nitric oxide(NO) assay, MTT assay and DPPH assay were performed. In addition, Western blotting and real time PCR were used to determine protein expression, and gene expression, respectively. HBE significantly inhibited NO production without observable cytotoxicity. In addition, HBE attenuated inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX-2) and phospho (p)-ERK protein expressions in LPS(0.1㎍/ml) stimulated RAW264.7 cells. On the other hand, HBE alone up-regulated HO-1 and Nrf-2 expressions, which mediated HBE's anti-inflammatory effect in RAW264.7 cells. Finally, HBE up-regulated HO-1 and impaired ERK1/2 signaling pathways, and thus it may provide protection against cellular oxidation and inflammation.

Anti-inflammatory Activities of an Ethanol Extract of Sargassum macrocarpum in Lipopolysaccharide (LPS)-stimulated RAW 264.7 Macrophages (Lipopolysaccaride로 유도된 Raw 264.7 세포에서 큰열매모자반 에탄올 추출물의 항염증 활성)

  • Cheon, Ji Min;Kim, Hyang Suk;Choi, Eun Ok;Kwon, Da Hye;Choi, Yung Hyun;Kim, Byung Woo;Hwang, Hye Jin
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1437-1444
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    • 2017
  • Sargassum macrocarpum is a widely distributed marine brown algae found in the North Pacific. The objective of this study was to evaluate the anti-inflammatory activity of an ethanol extract of S. macrocarpum (EESM). First, we investigated the anti-inflammatory activities of EESM in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. EESM treatment suppressed nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production and inhibited the expressions of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, the expression of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-1 beta ($IL-1{\beta}$), was decreased in a dose dependent manner. Investigation of the signaling pathways of nuclear factor kappa B ($NF-{\kappa}B$), phosphoinositide-3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) revealed suppression of $NF-{\kappa}B$ translocation from the cytosol to nucleus by EESM treatment. The phosphorylation of the Akt and ERK proteins was also inhibited by EESM treatment. EESM treatment also stimulated the expression of the heme oxygenase-1 (HO-1) enzyme and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2). These results suggest that EESM has anti-inflammatory activity and could have potential uses in the field of nutraceuticals.

Attenuation of Lipopolysaccharide-induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid Phosphate in RAW 264.7 Macrophages (RAW 264.7 대식세포에서 lipopolysaccharide 자극에 의한 염증성 및 산화적 스트레스에 미치는 5-aminolevulinic acid phosphate의 영향)

  • Ji, Seon Yeong;Kim, Min Yeong;Hwangbo, Hyun;Lee, Hyesook;Hong, Su Hyun;Cha, Hee-Jae;Kim, Heui-Soo;Kim, Suhkmann;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.9
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    • pp.818-826
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    • 2021
  • 5-Aminolevulinic acid phosphate (5-ALA-p) is a substance obtained by eluting 5-ALA (a natural delta amino acid) with aqueous ammonia, adding phosphoric acid to the eluate, and then adding acetone to confer properties suitable for use in photodynamic therapy applications. However, its pharmacological efficacy, including potential mechanisms of antioxidant and anti-inflammatory reactions, remains unclear. This study aimed to investigate the effects of 5-ALA-p on oxidative and inflammatory stresses in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our data showed that 5-ALA-p significantly inhibited excessive phagocytic activity via LPS and attenuated oxidative stress in LPS-treated RAW 264.7 cells. Furthermore, 5-ALA-p improved mitochondrial biogenesis reduced by LPS, suggesting that 5-ALA-p restores mitochondrial damage caused by LPS. Additionally, 5-ALA-p significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, which are associated with the inhibition of inducible NO synthase and respective cytokine expression. Furthermore, 5-ALA-p reduced the nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited phosphorylation of mitogen-activated protein kinases (MAPKs), indicating that the anti-inflammatory effect of 5-ALA-p is mediated through the suppression of NF-κB and MAPK signaling pathways. Based on these results, 5-ALA-p may serve as a potential candidate to reduce inflammation and oxidative stress.

Immune-enhancing and Anti-inflammatory Effects of HK Shiitake Mushroom Mycelium (HKSMM) using Balb/c Mice (Balb/c 마우스를 이용한 HK 표고버섯 균사체(HKSMM)의 면역증강 및 항염효과)

  • Kim, Hun Hwan;Ha, Sang Eun;Park, Min Young;Jeong, Se Hyo;Bhagwan, Bhosale Pritam;Abuyaseer, Abusaliya;Kim, Jeong Ok;Ha, Yeong Lae;Kim, Gon Sup
    • Journal of Life Science
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    • v.32 no.6
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    • pp.447-454
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    • 2022
  • In this study, we confirmed the effect of HK shiitake mushroom mycelium (HKSMM) on immune enhancement in Balb/c mice. Experimental animals were divided into five groups: negative control (NC), positive control (PC; 1,000 mg/100 g; AHCC), T1 (500 mg/100 g; HKSMM), T2 (1,000 mg/100 g; HKSMM), and T3 (2,000 mg/100 g; HKSMM), and dissection was performed at four and six weeks. COX-2 and iNOS concentrations were significantly lower in the six-week experimental group than in the control group, and the NO results were also similar. Results of the confirmation of the factors related to the NF-κB (p-p65 and p-IκBα) and MAPK (pERK, pJNK, and p38) signaling pathways revealed that the HKSMM-fed experimental group significantly decreased compared with the control group. A comparative analysis of the number and size of white pulp in the spleen tissue showed that those of the experimental group were significantly higher than those of the control group in a concentration-dependent manner. These results suggest that HKSMM has both immune-enhancing and anti-inflammatory effects in Balb/c mice, indicating that it can be used as a health functional food ingredient.