• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.379-386
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• 2024

Basophils and mast cells are specialized effector cells in allergic reactions. Haliotis discus hannai (abalone), is valuable seafood. Abalone male viscera, which has a brownish color and has not been previously reported to show anti-allergic activities, was extracted with acetone. Six different acetone/hexane fractions (0, 10, 20, 30, 40, and 100%) were obtained using a silica column via β-hexosaminidase release inhibitory activity-guided selection in phorbol myristate acetate and a calcium ionophore, A23187 (PMACI)-induced human basophils, KU812F cells. The 40% acetone/hexane fraction (A40) exhibited the strongest inhibition of PMACI-induced-β-hexosaminidase release. This fraction dose-dependently inhibited reactive oxygen species (ROS) production and calcium mobilization without cytotoxicity. Western blot analysis revealed that A40 down-regulated PMACI-induced MAPK (ERK 1/2, p-38, and JNK) phosphorylation, and the NF-κB translocation from the cytosol to membrane. Moreover, A40 inhibited PMACI-induced interleukin (IL)-1β, IL-6, and IL-8 production. Anti-allergic activities of A40 were confirmed based on inhibitory effects on IL-4 and tumor necrosis factor alpha (TNF-α) production in compound (com) 48/80-induced rat basophilic leukemia (RBL)-2H3 cells. A40 inhibited β-hexosaminidase release and cytokine production such as IL-4 and TNF-α produced by com 48/80-stimulated RBL-2H3 cells. Furthermore, it's fraction attenuated the IgE/DNP-induced passive cutaneous anaphylaxis (PCA) reaction in the ears of BALB/c mice. Our results suggest that abalone contains the active fraction, A40 is a potent therapeutic and functional material to treat allergic diseases.

• 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.

• Journal of Periodontal and Implant Science
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• v.47 no.5
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• pp.273-291
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• 2017

Purpose: Although static magnetic fields (SMFs) have been used in dental prostheses and osseointegrated implants, their biological effects on osteoblastic and cementoblastic differentiation in cells involved in periodontal regeneration remain unknown. This study was undertaken to investigate the effects of SMFs (15 mT) on the osteoblastic and cementoblastic differentiation of human osteoblasts, periodontal ligament cells (PDLCs), and cementoblasts, and to explore the possible mechanisms underlying these effects. Methods: Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity, mineralized nodule formation based on Alizarin red staining, calcium content, and the expression of marker mRNAs assessed by reverse transcription polymerase chain reaction (RT-PCR). Signaling pathways were analyzed by western blotting and immunocytochemistry. Results: The activities of the early marker ALP and the late markers matrix mineralization and calcium content, as well as osteoblast- and cementoblast-specific gene expression in osteoblasts, PDLCs, and cementoblasts were enhanced. SMFs upregulated the expression of Wnt proteins, and increased the phosphorylation of glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$) and total ${\beta}-catenin$ protein expression. Furthermore, p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK), and nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) pathways were activated. Conclusions: SMF treatment enhanced osteoblastic and/or cementoblastic differentiation in osteoblasts, cementoblasts, and PDLCs. These findings provide a molecular basis for the beneficial osteogenic and/or cementogenic effect of SMFs, which could have potential in stimulating bone or cementum formation during bone regeneration and in patients with periodontal disease.

• Journal of Periodontal and Implant Science
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• v.48 no.2
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• pp.70-83
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• 2018

Purpose: The aim of this study was to evaluate the capacity of single and combined applications of the bark of the stems and roots of Magnolia officinalis Rehd. et Wils. (Magnoliae Cortex) and Zea mays L. (maize) to modulate inflammation in RAW 264.7 cells stimulated with Porphyromonas gingivalis. Methods: RAW 264.7 cells were stimulated with P. gingivalis, and Magnoliae Cortex and/or maize was added. Cytotoxicity and the capacity to modulate inflammation were determined with a methylthiazol tetrazolium (MTT) assay, nitrite production, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results: Treatment with Magnoliae Cortex and/or maize inhibited nuclear transcription factor ${\kappa}B$ ($NF-{\kappa}B$) pathway activation and nuclear p44/42 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthase (iNOS) protein expression in P. gingivalis-stimulated RAW 264.7 cells. Moreover, the treatments suppressed cytokines (prostaglandin $E_2$ [$PGE_2$], interleukin $[IL]-1{\beta}$, and IL-6) and nitrite production. Conclusions: Both Magnoliae Cortex and maize exerted an anti-inflammatory effect on P. gingivalis-stimulated RAW 264.7 cells, and this effect was more pronounced when the extracts were combined. These findings show that these extracts may be beneficial for slowing the progression of periodontal disease.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.390-399
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• 2014

Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.

• 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.

• Journal of Nutrition and Health
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• v.41 no.3
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• pp.224-231
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• 2008

We examined the effect of indole-3-carbinol (I3C, $C_9H_9NO$), an autolysis product of a glucosinolate and a glucobrassicin in vegetables, on MMP-2, -9 activities and TIMP-l and -2 inductions via microtubule-associated protein kinase (MAPK) signaling pathway in prostate cancer cell line, PC3 cells. Our results indicated that I3C inhibited cell growth of PC3 cells in dose (0,50, 100 ,${\mu}M$) and time (0,24,48 and 72 h) dependent manners. Using gelatin zymography for MMP activity, we demonstrated that I3C significantly decrease MMP-2 and -9 activities in PC3 cells. We also observed that I3C decreased the proteins and mRNA levels of MMP-2 and -9 in PC3 cells as well. Inversely, expressions of TIMP-l and -2 protein and mRNA in PC3 cells were increased by I3C in a dose dependent manner. In another experiment, we showed that I3C inhibited PC3 cells invasiveness by using marigel invasion assay and we also found that I3C suppressed MMP transcriptional activity by MAPK signaling pathways. Taken together, our results suggest that I3C may contribute to the potential beneficial food component to prevent the cancer metastasis in prostate cancer cells. (KoreanJNutr2008; 41(3): 224~23I)

• BMB Reports
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• v.45 no.3
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• pp.171-176
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• 2012

Receptor activator of NF-${\kappa}B$ ligand (RANKL) triggers the differentiation of bone marrow-derived monocyte/macrophage precursor cells (BMMs) of hematopoietic origin into osteoclasts through the activation of mitogen-activated protein (MAP) kinases and transcription factors. Recently, reactive oxygen species (ROS) and antioxidant enzymes were shown to be closely associated with RANKL-mediated osteoclast differentiation. Although glutaredoxin2 (Glrx2) plays a role in cellular redox homeostasis, its role in RANKL-mediated osteoclastogenesis is unclear. We found that Glrx2 isoform b (Glrx2b) expression is induced during RANKLmediated osteoclastogenesis. Over-expression of Glrx2b strongly enhanced RANKL- mediated osteoclastogenesis. In addition, Glrx2b-transduced BMMs enhanced the expression of key transcription factors c-Fos and NFATc1, but pre-treatment with SB203580, a p38-specific inhibitor, completely blocked this enhancement. Conversely, down-regulation of Glrx2b decreased RANKL- mediated osteoclastogenesis and the expression of c-Fos and NFATc1 proteins. Also, Glrx2b down-regulation attenuated the RANKL-induced activation of p38. Taken together, these results suggest that Glrx2b enhances RANKL-induced osteoclastogenesis via p38 activation.

• Journal of Ginseng Research
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• v.31 no.4
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• pp.181-190
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• 2007

Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-${\kappa}B$, and expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-${\kappa}B$ activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.

• Journal of Nutrition and Health
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• v.54 no.3
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• pp.321-333
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• 2021

Purpose: Reflux esophagitis is a disease caused by the reflux of stomach contents and stomach acid etc. into the esophagus due to defect in the lower esophageal sphincter and is currently increasing worldwide. This study was conducted to evaluate the effect of a mixture of Citrus Reticulata and Scutellariae Radix (CS) extract on acute reflux esophagitis in rats. Methods: Rats were divided into five groups for examination: normal group (Normal, n = 8), water-treated acute reflux esophagitis rats (Control, n = 8), tocopherol 30 mg/kg body weight-treated acute reflux esophagitis rats (Toco, n = 8), CS 100 mg/kg body weight-treated acute reflux esophagitis rats (CS100, n = 8), CS 200 mg/kg body weight-treated acute reflux esophagitis rats (CS200, n = 8). The experimental groups were administrated of each treatment compounds and after 90 min, acute reflux esophagitis was induced through surgery. Rats were sacrificed 5 h after surgery. We measured the level of reactive oxygen species (ROS) in serum and analyzed the expression of nicotinamide adenine dinucleotide phosphate, inflammatory, and tight junction-related proteins by western blot in the esophageal tissues. Results: CS administration significantly protected the esophageal mucosal damage due to reflux esophagitis, and the level of ROS in the serum was significantly reduced with CS administration as compared to Control. In addition, CS administration significantly suppressed mitogen-activated protein kinase (MAPK or MAP kinase) and nuclear factor-kappa B (NF-κB) pathways and increased protein expressions of tight junction protein. Conclusion: These results suggest that the CS not only regulates the expression of inflammatory proteins by inhibiting oxidative stress, but also reduces damage to the esophageal mucosa by inhibiting the expression of tight junction proteins.