• Journal of Microbiology and Biotechnology
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• v.29 no.5
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• pp.820-826
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• 2019

This study evaluated the anti-inflammatory potential of a grasshopper ketone (GK) isolated from the brown alga Sargassum fulvellum on lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophage cell line. GK was isolated and purified from the n-hexane fraction and its structure was verified on the basis of NMR spectroscopic data. GK up to $100{\mu}g/ml$ is not cytotoxic to RAW 264.7, and is an effective inhibitor of LPS-induced NO production in RAW 264.7 cells. The production of pro-inflammatory cytokines, including IL-6, $IL-1{\beta}$, and $TNF-{\alpha}$ was found significantly reduced in $0.1-100{\mu}g/ml$ dose ranges of GK treatment (p < 0.05). We confirmed the dose-dependent and significant inhibition of iNOS and COX-2 proteins expression. In addition, it has been shown that GK induces anti-inflammatory effects by inhibiting MAPKs (ERK, JNK, and p38) and $NF-{\kappa}B$ p65 phosphorylation. Our results show that the anti-inflammatory properties of GK may be due to the inhibition of the $NF-{\kappa}B$ and MAPKs pathways, which are associated with the attenuation of cytokine secretion.

• Journal of Microbiology and Biotechnology
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• v.29 no.5
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• pp.704-712
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• 2019

Although nanometric dead Lactobacillus plantarum has emerged as a potentially important modulator of immune responses, its underlying mechanism of action has not been fully understood. This study aimed to identify the detailed biochemical mechanism of immune modulation by micronized and heat-treated L. plantarum LM1004 (MHT-LM1004, <$1{\mu}m$ in size). MHT-LM1004 was prepared from L. plantarum LM1004 via culture in a specifically designed membrane bioreactor and heat treatment. MHT-LM1004 was shown to effectively induce the secretion of $TNF-{\alpha}$ and IL-6 and the mRNA expression of inducible nitric oxide synthase (iNOS). MHT-LM1004 enhanced the expression of TLR-2, phosphorylation of MAPKs (ERK), and nuclear translocation of $NF-{\kappa}B$ in a dose-dependent manner. Oral administration of MHT-LM1004 ($4{\times}10^9$ or $4{\times}10^{11}cells/kg$ mouse body weight) increased the splenocyte proliferation and serum cytokine levels. These results suggested that MHT-LM1004 effectively enhances early innate immunity by activating macrophages via the TLR-2/MAPK/$NF-{\kappa}B$ signalling pathway and that this pathway is one of the major routes in immune modulation by the Lactobacillus species.

• Laboraroty Animal Research
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• v.33 no.1
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• pp.40-47
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• 2017

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-${\alpha}$, interleukin (IL)-6 and IL-$1{\beta}$ in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.3
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• pp.201-208
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• 2022

Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.

• The Korea Journal of Herbology
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• v.32 no.2
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• pp.65-75
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• 2017

Objectives : This study aimed to evaluate the protective effect of Orostachydis Herba (OH) and Fermented OH (OHF) against the acute liver injury by lipopolysaccharide (LPS). Methods : OHF by 4 lactic bacteria such as (Lactobacillus hilgardii (OHF1), Leuconostoc mesenteroides (OHF2), Pediococcus acidilactici (OHF3), Saccharomyces cerevisiae (OHF4)) were prepared. Samples were selected to OHF0, OHF2, OHF3 based on UPLC analysis, DPPH, ABTS radical scavenging activities. To evaluate the protective effect of OHF on liver injury mice, ICR mice were divided into 5 groups: Normal mice (Nor), LPS (20 mg/kg) treated mice (Veh), administrated OHF0, OHF2 OHF3 200 mg/kg body weight during 8 days before LPS injection. Serum and liver were collected 24 hours after LPS injection. Results : The activity was high in order of OHF0 and OHF3 in DPPH and ABTS radical scavenging activities. The quercetin contents for bioactive ingredient of OH was 5.39, kaempferol contents was 9.94 by UPLC analysis. The LPS-treated vehicle group significantly increased liver weight, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum. In contrast, administrated OHF3 group decreased liver weight, AST, ALT. In addition, OHF3 groups reduced the elevated levels of reactive oxygen species (ROS) in serum and tissues. Moreover, AP-1, iNOS and COX-2 were significantly decreased in OHF2 and OHF3. But $NF-{\kappa}B$ p65 and $TNF-{\alpha}$ only showed a significant reduction in OHF3. Conclusions : Therefore, these results suggest that fermented Orostachydis Herba might be protective effect on liver injury through anti-oxidant effect.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.4
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• pp.524-531
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• 2015

Antioxidant activities and in vitro anticancer effects of bamboo salt doenjang on HT-29 human colon cancer cells were studied. 3Y3B-D (three-year fermentation using three-time baked bamboo salt doenjang), 3Y9B-D (three-year fermentation using nine-time baked bamboo salt doenjang), 6Y3B-D (six-year fermentation using three-time baked bamboo salt doenjang), and 6Y9B-D (six-year fermentation using nine-time baked bamboo salt doenjang) were compared to C-D (commercial doenjang) and 3B-S (cooked soy beans prepared using three-time baked bamboo salt). There were no differences between experimental groups in pH, amino-type nitrogen, or ammonia-type nitrogen levels. 6Y9B-D showed the highest antioxidative effect, followed by 6Y3B-D, 3Y9B-D, and 3Y3B-D, in order. 6Y9B-D showed the highest total polyphenol concentration. 6Y9B-D showed the highest anticancer effect, as determined by MTT assay, as well as levels of the pro-inflammatory cytokines including TNF-${\alpha}$, IL-6, iNOS, and COX-2, followed by 6Y3B-D, 3Y9B-D, and 3Y3B-D, in order. From the results above, 6Y9B-D showed the highest antioxidative and anticancer effects, followed by 6Y3B-D, 3Y9B-D, 3Y3B-D, C-D, and 3B-S.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.4
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• pp.477-484
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• 2014

The purpose of this study was to examine the anti-inflammatory effects of ginger and processed (Beopje) ginger on colitis induced by 2.5% dextran sulfate sodium (DSS) in Balb/c mice. Beopje means a process that herbal medicines are treated by a specific Korean traditional method in order to obtain better pharmacological effects. Mice were fed saline or two different doses of ethanol extracts (ginger and processed (Beopje) ginger) once a day for 14 days. Colitis was induced from day 7 to 14 via administration of 2.5% DSS in drinking water. Experimental animals were divided into four groups: Nor (Normal, 200 ${\mu}L$ of saline without 2.5% DSS-treated group), Con (Control, 200 ${\mu}L$ of saline and 2.5% DSS treated group), G (500 mg/kg of ginger and 2.5% DSS treated group), and BG (500 mg/kg of Beopje ginger and 2.5% DSS treated group). Body weights of both ginger-administered groups increased compared to the control. Colon length increased to 7.6, and 8.0 cm in the G and BG groups, respectively, whereas that of control was 5.7 cm. Histological colon injury induced by DSS-induced colitis was reduced (P<0.05). In serum and DSS-treated colon tissues, mRNA expression levels of IFN-${\gamma}$, IL-6, TNF-${\alpha}$, and IL-12 of the Beopje ginger-treated group were significantly suppressed compared to those of the ginger-treated groups. Expression levels of iNOS and COX-2 of the Beopje ginger-treated group were significantly reduced compared to those of the ginger-treated groups (P<0.05), and BG showed stronger anti-inflammatory effects on colitis. These results indicated that ginger exerted anti-inflammatory effects on DSS-induced colitis in mice, and its effects could be increased through Beopje.

• Journal of Life Science
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• v.24 no.11
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• pp.1157-1167
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• 2014

In order to compare the anti-inflammatory effects of five selected cereal grains-proso millet, hwanggeumchal sorghum, foxtail millet, barnyard millet, and adlay-the inhibitory activities of 80% ethanol (EtOH) extracts obtained from the individual grains on lipopolysaccharide (LPS)-induced nitric oxide (NO) generation were investigated in RAW264.7 cells. The EtOH extract of barnyard millet (Echinochloa crus-galli var. frumentacea) grains exhibited more potent anti-inflammatory activity than that of the other grains. When the EtOH extract of barnyard millet grains was sequentially fractionated with n-hexane, methylene chloride (MC), ethyl acetate (EtOAc), and n-butanol, the majority of the anti-inflammatory activity was detected in the MC fraction, followed by the EtOAc fraction. Pretreatment with the MC fraction caused downregulation of the expression levels of iNOS- and COX-2-specific transcripts and proteins, as well as proinflammatory cytokine gene transcripts (IL-$1{\beta}$, IL-6, and TNF-${\alpha}$) in LPS-stimulated RAW264.7 cells. Additionally, the MC fraction could suppress not only the LPS-induced nuclear translocation of cytosolic NF-kB, but also the LPS-induced activation of MAPKs, such as ERK, JNK, and p38MAPK. Further analysis of the MC fraction by HPLC identified kaempferol, biochanin A, and formononetin as the major phenolic components. Both kaempferol and biochanin A, but not formononetin, could exert anti-inflammatory effect at the same concentrations as those of the MC fraction. Consequently, these results indicate that kaempferol and biochanin A are among the most effective anti-inflammatory phenolic components in barnyard millet grains. This finding suggests that barnyard millet grains and the MC extract enriched in kaempferol and biochanin A could be beneficial functional food sources that have an anti-inflammatory effect.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.11
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• pp.1612-1620
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• 2015

Inflammation is a complex process involving a variety of immune cells, which defend the body from harmful stimuli. However, pro-inflammatory cytokines and inflammatory mediators can also exacerbate diseases such as cancer. Onion peel contains several phenolic compounds, including quercetin at an amount 20 times greater in peel than edible flesh. Therefore, in this study, the anti-inflammatory effects of onion peel ethanol extract (OPEE) were investigated lipopolysaccharide-induced inflammatory response. In our results, NO production decreased in a dose-dependent manner. Secretion of IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$ was suppressed by 44%, 53%, and 60% respectively, at $100{\mu}g/mL$. Moreover, OPEE also suppressed expression of COX-2, iNOS, $NF-{\kappa}B$, and MAPKs in a dose-dependent manner. Formation of mice ear edema was reduced at the highest dose tested compared to the control, and reduction of ear thickness was observed in the histological analysis as well. In the acute toxicity test, no morality was observed in mice administered 5,000 mg/kg body weight of OPEE over a 2-week observation period. These results suggest that OPEE may have significant effects on inflammatory factors and be a potential anti-inflammatory material.

• Molecules and Cells
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• v.38 no.10
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• pp.886-894
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• 2015

Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-$Gu{\acute{e}}rin$) activates disabled $na{\ddot{i}}ve$ macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-${\alpha}$), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-$1{\beta}$), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-${\beta}$) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.