• BMB Reports
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• v.48 no.10
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• pp.559-564
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• 2015

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-$\alpha$-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-$\alpha$-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-$\alpha$ significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-$\alpha$-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-$\alpha$-induced invasion of LNCaP cells. Compared to untreated controls, TNF-$\alpha$-stimulated LNCaP cells showed a significant increase in nuclear factor-${\kappa}B$ (NF-${\kappa}B$) luciferase activity. However, mangiferin treatment markedly decreased TNF-$\alpha$-induced NF-${\kappa}B$ luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-${\kappa}B$ subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-${\kappa}B$-mediated MMP-9 expression.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.71-78
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• 2020

Lactobacillus sakei S1 strongly inhibits the expression of interleukin (IL)-6 and IL-1β in lipopolysaccharide-induced peritoneal macrophages by a mechanism for which lactic acid bacteria from kimchi that inhibit tumor necrosis factor-alpha (TNF-α) were isolated. Therefore, we further evaluated the protective effect of this strain on the colitis mouse model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS significantly elevated myeloperoxidase (MPO) expression, macroscopic scores, and colon shortening. Oral L. sakei S1 administration resulted in reduction of TNBS-induced loss in body weight, colon shortening, MPO activity, expression of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB). L. sakei S1 inhibited the expression of inflammatory cytokines IL-1β, IL-6 and TNF-α, induced by TNBS, but enhanced IL-10 expression. L. sakei S1 showed resistance to artificial digestive juices and adherence to intestinal epithelial Caco-2 cells. Thus, L. sakei S1 may inhibit the NF-κB pathway and be used in functional food to treat colitis.

• Genomics & Informatics
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• v.20 no.1
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• pp.7.1-7.13
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• 2022

2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor κB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

• Korean Journal of Plant Resources
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• v.32 no.6
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• pp.705-713
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• 2019

Avocado, superfood, contains a variety of essential nutrients and phytochemicals. The purpose of this study was to explore whether avocado could modulate skin inflammation in vivo. We elucidated the pharmacological effects of avocado on compound 48/80- or histamine-induced scratching behaviors and 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in mice. Additionally, we investigated the anti-inflammatory activity of avocado and its underlying mechanism including its effect on the expression levels of inflammatory-related genes and nuclear factor-κB (NF-κB) in DNCB-induced AD-like skin lesions. The findings of this study demonstrate that avocado attenuated AD-clinical symptoms including itching, eczematous, erythema and dryness and histamine levels in mice. Moreover, avocado suppressed both inflammatory cytokines expression as well as NF-κB and caspase-1 activation in AD-like skin lesions in mice. Taken together, these results demonstrate that avocado may be a potential candidate for treating skin inflammatory diseases like AD.

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.495-509
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• 2003

Background : Neutrophil-mediated inflammation is usually self-limiting, because neutrophils have a remarkably short life span. Prolonged neutrophil survival, which is caused by decreased spontaneous apoptosis, leads to persistent inflammation in sepsis. Because many inflammatory cytokines, which generate signals that delay apoptosis, are regulated by nuclear factor-${\kappa}B$ transcription factor, we hypothesized that nuclear factor-${\kappa}B$ might be related to the reduced neutrophil apoptosis observed in sepsis. Methods : Neutrophils of healthy volunteers and sepsis patients were freshly isolated from venous blood. Neutrophil apoptosis was assayed with two approaches : by counting apoptotic cells under a microscope and by flow cytometry using Annexin V. The activity of nuclear factor-${\kappa}B$ was assessed by immunofluorescent staining or electrophoretic mobility shift assay. Expression of X-linked inhibitor of apoptosis was measured by western blot assay. Results : We confirmed reduced spontaneous neutrophil apoptosis in patients with sepsis. The number of apoptotic neutrophils in patients with sepsis increased to the level of that in healthy controls after cycloheximide treatment, suggesting that decreased spontaneous neutrophil apoptosis is dependent on de novo protein synthesis. In patients with sepsis, basal neutrophil nuclear factor-${\kappa}B$ was activated compared to the level in healthy controls. Moreover, a blockade of nuclear factor-${\kappa}B$ activity reversed the decreased spontaneous neutrophil apoptosis in sepsis patients. Meanwhile, X-linked inhibition of apoptosis expression, which is regulated by nuclear factor-${\kappa}B$, decreased 24 hours after incubation in healthy persons, but persisted for 24 hours in patients with sepsis. Conclusion : These observations suggest that the reduced spontaneous neutrophil apoptosis observed in patients with sepsis may be related to the induction of survival protein by nuclear factor-${\kappa}B$.

• Korean Journal of Plant Resources
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• v.34 no.3
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• pp.216-222
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• 2021

Ulcerative colitis (UC) is an inflammatory bowel disease and a chronic gastrointestinal disorder. Rubi Fructus (RF), the fruit of Rubus coreanus Miquel, is known to exert several pharmacological effects including anti-oxidative, anti-obesity and anti-inflammatory properties. However, the improving effect and mechanism of RF on intestinal inflammation is not been fully understood. The purpose of this study was to investigate the regulatory effect of RF on dextran sulfate sodium (DSS)-induced colitis in mice. We evaluated the effects of RF on DSS-induced clinical signs by analyzing weight loss and colon length. The inhibitory effects of RF on inflammatory mediators such as prostaglandin E₂ (PGE₂), cyclooxygenase (COX)-2, as well as the activation of nuclear factor-κB (NF-κB), were determined in colitis tissue. Our data indicated that mice treated with DSS showed clinical symptoms of colitis, including weight loss, colon length decrease and diarrhea. However, we observed that RF treatment significantly improved these clinical symptoms of weight loss, colon length decrease and diarrhea induced by DSS. RF inhibited the enhanced levels of COX-2 and PGE₂ caused by DSS. We also showed that the anti-inflammatory mechanism of RF by suppressing the activation of NF-kB in DSS-treated colon tissues. Collectively, the findings of this study indicate the prospect of developing new drugs from RF for UC treatment.

• International Journal of Oral Biology
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• v.46 no.1
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• pp.51-59
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• 2021

Periodontal disease is an inflammatory disease that affects the destruction of the bone supporting the tooth and connective tissues surrounding it. Periodontal ligament fibroblasts (PDLFs) induce overexpression of matrix metalloproteinase (MMP) involved in periodontal disease's inflammatory destruction. Osteoclasts take part in physiological bone remodeling, but they are also involved in bone destruction in many kinds of bone diseases, including osteoporosis and periodontal disease. This study examined the effect of baicalin on proteolytic enzymes' production and secretion of inflammatory cytokines in PDLFs and RAW 264.7 cells under the lipopolysaccharide (LPS)-induced inflammatory conditions. Baicalin inhibited the expression of the protein, MMP-1 and MMP-2, without affecting PDLFs' cell viability, suggesting its possibility because of the inhibition of phosphorylation activation of mitogen-activated protein kinase's p38, and the signal transduction process of nuclear factor κB (NFκB)-related protein. Also, baicalin reduced the expression of MMP-8 and MMP-9 in RAW 264.7 cells. This reduction is thought to be due to the inhibition of the signal transduction process of NFκB-related proteins affected by inhibiting p65RelA phosphorylation. Also, baicalin inhibited the secretion of nitric oxide and interleukin-6 induced by LPS in RAW 264.7 cells. These results suggest that baicalin inhibits connective tissue destruction in periodontal disease. The inhibition of periodontal tissue destruction may be a therapeutic strategy for treating inflammatory periodontal-diseased patients.

• Molecules and Cells
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• v.26 no.5
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• pp.486-489
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• 2008

Curcumin (diferuloylmethane), a pigment derived from turmeric, has anti-oxidant and anti-inflammatory activities. Accumulating evidence points to a biochemical link between increased oxidative stress and reduced bone density. Osteoclast formation was evaluated in co-cultures of bone marrow stromal cells (BMSC) and whole bone marrow cells (BMC). Expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) was analyzed at the mRNA and protein levels. Exposure to curcumin led to dose-dependent suppression of osteoclastogenesis in the co-culture system, and to reduced expression of RANKL in $IL-1{\alpha}$-stimulated BMSCs. Addition of RANKL abolished the inhibition of osteoclastogenesis by curcumin, whereas the addition of prostaglandin $E_2$ ($PGE_2$) did not. The decreased osteoclastogenesis induced by curcumin may reduce bone loss and be of potential benefit in preventing and/or attenuating osteoporosis.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.61-73
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• 2023

Esophageal squamous cell carcinoma (ESCC) is a kind of malignant tumor with high incidence and mortality in the digestive system. The aim of this study is to explore the function of lnc-ABCA12-3 in the development of ESCC and its unique mechanisms. RT-PCR was applied to detect gene transcription levels in tissues or cell lines like TE-1, EC9706, and HEEC cells. Western blot was conducted to identify protein expression levels of mitochondrial apoptosis and toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. CCK-8 and EdU assays were carried out to measure cell proliferation, and cell apoptosis was examined by flow cytometry. ELISA was used for checking the changes in glycolysis-related indicators. Lnc-ABCA12-3 was highly expressed in ESCC tissues and cells, which preferred it to be a candidate target. The TE-1 and EC9706 cells proliferation and glycolysis were obviously inhibited with the downregulation of lnc-ABCA12-3, while apoptosis was promoted. TLR4 activator could largely reverse the apoptosis acceleration and relieved the proliferation and glycolysis suppression caused by lnc-ABCA12-3 downregulation. Moreover, the effect of lnc-ABCA12-3 on ESCC cells was actualized by activating the TLR4/NF-κB signaling pathway under the mediation of exosome. Taken together, the lnc-ABCA12-3 could promote the proliferation and glycolysis of ESCC, while repressing its apoptosis probably by regulating the TLR4/NF-κB signaling pathway under the mediation of exosome.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.109-116
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• 2020

BACKGROUND/OBJECTIVES: Excessive intake of simple sugars induces obesity and increases the risk of inflammation. Thus, interest in alternative sweeteners as a sugar substitute is increasing. The purpose of this study was to determine the effect of saccharin on inflammation in 3T3-L1 adipocytes. MATERIALS/METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes. The adipocytes were treated with saccharin (0, 50, 100, and 200 ㎍/mL) for 24 h. Inflammation was induced by exposure of treated adipocytes to lipopolysaccharide (LPS) for 18 h and cell proliferation was measured. The concentration of nitric oxide (NO) was measured by using Griess reagent. Protein expressions of nuclear factor kappa B (NF-κB) and inhibitor κB (IκB) were determined by western blot analysis. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were determined by real-time PCR. RESULTS: Compared with the control group, the amount of NO and the mRNA expression of iNOS in the LPS-treated group were increased by about 17.6% and 46.9%, respectively, (P < 0.05), and those parameter levels were significantly decreased by saccharin treatment (P < 0.05). Protein expression of NF-κB was decreased and that of IκB was increased by saccharin treatment (P < 0.05). Saccharin decreased the mRNA expression of COX-2 and the inflammation cytokines (IL-1β, IL-6, MCP-1, and TNF-α) (P < 0.05). CONCLUSIONS: The results of this study suggest that saccharin can inhibit LPS-induced inflammatory responses in 3T3-L1 adipocytes via the NF-κB pathway.