• Biomedical Science Letters
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• v.14 no.3
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• pp.147-155
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• 2008

In previous works, we found that solvent extract of Opuntia humifusa Raf., a member of the lactaceae family, displayed potent anti-oxidative and anti-inflammatory activities. Thus, all solvent fractions, except for the water layer, showed potent scavenging effects. According to activity-guided fractionation, one of active radical scavenging principles in the ethyl acetate fraction was found to be taxifolin. In this study, we investigated whether taxifolin showed anti-oxidative activity. In addition, taxifolin modulated nitric oxide (NO) release and the expression of pro-inflammatory cytokine mRNA such as interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-${\alpha}$. Taxifolin showed potent anti-oxidant activity with the $IC_{50}\;of\;8.5{\pm}1.4\;and\;9.3{\pm}1.0{\mu}M$ using xanthine/xanthine oxidase (XO) assay and 2,2-Diphenyl-lpicrylhydrazyl radical (DPPH) assay, respectively. We next determined the role of taxifolin on the immunomodulating activity using murine macrophage cell line RAW264.7 cells. Taxifolin dose-dependently inhibited NO production in lipopolysaccharide (LPS)-activated RAW264.7. It also significantly blocked the expression of inducible NO synthase (iNOS) mRNA in the LPS-stimulated RAW264.7 cells. In addition, taxifolin potently suppressed the expression of IL-$1{\beta}$, IL-6 and GM-CSF mRNA in LPS-activated RAW264.7 cells, but not that of TNF-${\alpha}$ Moreover, taxifolin significantly inhibited the transcriptional activity of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein -1 (AP-1). These results suggest that taxifolin may downregulate inflammatory iNOS, IL-$1{\beta}$, IL-6 and GM-CSF gene expressions through inhibition of NF-K and AP-1 activation in LPS-stimulated RAW264.7 cells.

• Journal of dental hygiene science
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• v.17 no.1
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• pp.81-86
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• 2017

Bacterial infection and smoking are an important risk factors involved in the development and progression of periodontitis. However, the signaling mechanism underlying the host immune response is not fully understood in periodontal lesions. In this study, we determined the expression of janus kinase (JAK)/signal transducer and activator of transcription (STAT) on Porphyromonas gingivalis lipopolysaccharide (LPS)- and nicotine-induced cytotoxicity and the production of inflammatory mediators, using osteoblasts. The cells were cultured with 5 mM nicotine in the presence of $1{\mu}g/ml$ LPS. Cell viability was determined using MTT assay. The role of JAK on inflammatory mediator expression and production, and the regulatory mechanisms involved were assessed via enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blot analysis. LPS- and nicotine synergistically induced the production of cyclooxgenase-2 (COX-2) and prostaglandin $E_2$ ($PGE_2$) and increased the protein expression of JAK/STAT. Treatment with an JAK inhibitor blocked the production of COX-2 and $PGE_2$ as well as the expression of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$ ($IL-1{\beta}$), and IL-6 in LPS- and nicotine-stimulated osteoblasts. These results suggest that JAK/STAT is closely related to the LPS- and nicotine-induced inflammatory effects and is likely to regulate the immune response in periodontal disease associated with dental plaque and smoking.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.363-369
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• 2011

The present study elucidated the effect of the selective inducible nitric oxide synthase (iNOS) inhibitor $N^6$-(1-iminoethyl)-L-lysine (L-NIL) on monosodium urate (MSU) crystal-induced inflammation and edema in mice feet. L-NIL (5 or 10 mg/kg/day) was administered intraperitoneally 4 h before injection of MSU (4 mg) into the soles of mice hindlimb feet. Twenty-four hours after MSU injection, foot thickness was increased by 160% and L-NIL pretreatment reduced food pad swelling in a dose dependent manner. Pretreatment of 10 mg/kg/day L-NIL significantly suppressed the foot pad swelling by MSU. Plasma level of nitric oxide (NO) metabolites and gene expression and protein level of iNOS in feet were increased by MSU, which was suppressed by L-NIL pretreatment. Similar pattern of change was observed in nitrotyrosine level. MSU increased the gene expression of tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-$1{\beta}$ and L-NIL pretreatment suppressed MSU-induced cytokines expression. The mRNA levels of superoxide dismutase and glutathione peroxidase1 were increased by MSU and L-NIL pretreatment normalized the gene expression. Phosphorylation of extracellular signal-regulated kinase 1/2 and p38 was increased by MSU, which was suppressed by L-NIL pretreatment. The mRNA levels of iNOS, TNF-${\alpha}$, and IL-$1{\beta}$ were increased by MSU in human dermal fibroblasts, C2C12 myoblasts, and human fetal osteoblasts in vitro, which was attenuated by L-NIL in a dose dependent manner. This study shows that L-NIL inhibits MSU-induced inflammation and edema in mice feet suggesting that iNOS might be involved in MSU-induced inflammation.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.369-377
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• 2018

Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin (4,2',4'-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their $6^{th}$ lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor ${\kappa}B$ ($NF-{\kappa}B$) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon ${\gamma}$ ($IFN-{\gamma}$) were evaluated through ELISA. The effects of ISL on the phosphorylation of $I{\kappa}B{\alpha}$, $IKK{\alpha}/{\beta}$ and p65 in $NF-{\kappa}B$ signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. $NF-{\kappa}B$ signaling was inhibited, in which the phosphorylation of p65, $I{\kappa}B{\alpha}$ and $IKK{\alpha}/{\beta}$ were suppressed whereas the level of $I{\kappa}B{\alpha}$ were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, $NF-{\kappa}B$, IL-4 and IL-10 in treating ST.

• Journal of Periodontal and Implant Science
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• v.35 no.3
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• pp.675-685
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• 2005

Bone resorption involves sequential stages of osteoclast precursor migration and differentiation of osteoclast precursors into multinucleated osteoclasts. Stromal cell derived factor (SDF)-1 is a chemotactic factor for osteoclast precursor migration. Matrix metalloproteinase (MMP)-9 is involved in migration of osteoclast precursors and activation of $interleukin(IL)-1{\beta}$. Alveolar bone destruction is a characteristic feature of periodontal disease. Treponema lecithinolyticum is a oral spirochete isolated from the periodontal lesions. The effect of lipopolysaccharide(LPS) from T. lecithinolyticum on expression of SDF-1 and MMP-9 was examined in cocultures of bone marrow cells and osteblasts derived from mouse calvariae. T. lecithinolyticum LPS increased expression of MMP-9 in the coculture. Polymyxin B, an inhibitor of LPS, abolished the increase of MMP-9 mRNA expression by LPS. LPS did not increase the expression of SDF-1, $IL-1{\beta}$ and tumor necrosis $factor(TNF)-{\alpha}$ mRNA in cocultures. Prostaglandin $E_2(PGE_2)$ up-regulated the expression of MMP-9 and NS398, an inhibitor of $PGE_2$ synthesis, down-regulated the induction of MMP-9 expression by T. lecitbinolyticm LPS. These results suggest that T. lecitbinolyticm LPS increases MMP-9 expression in bone cells via $PGE_2$ and that the induction of MMP-9 expression by T. lecitbinolyticm LPS is involved in alveolar bone destruction of periodontitis patients by the increase of osteoclast precursor migration and the activation of bone resorption-inducing cytokine.

• Microbiology and Biotechnology Letters
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• v.43 no.4
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• pp.391-395
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• 2015

We examined the anti-inflammatory effect and anti-tumor activity of Tetragonia tetragonioides crude extracts and fractions. The anti-inflammatory activity of T. tetragonioides was exuded through the inhibition of lipopolysaccharide (LPS, $1{\mu}g/ml$), induced nitric oxide (NO) and interleukin (IL)-$1{\beta}$ production. The production of IL-6 and tumor necrosis factor $(TNF)-{\alpha}$ also decreased in LPS induced RAW264.7 cells after treatment with polysaccharide (PS) fraction. Furthermore, the hexane (HX) fraction strongly inhibited the granulocytes macrophage-colony stimulating factor (GM-CSF) production. In ICR mice previously inoculated with Sarcoma 180, the life prolongation effects were 16.67% with an intraperitoneal injection of methanol (MeOH) extract and polysaccharide fraction at a dose of 100 mg/kg/day. The results are an important preliminary step toward the development of effective anti-inflammatory and anti-tumor agents using T. tetragonioides.

• Nutrition Research and Practice
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• v.16 no.5
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• pp.549-564
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• 2022

BACKGROUND/OBJECTIVES: Oxidative stress is caused by an imbalance between harmful free radicals and antioxidants. Long-term oxidative stress can lead to an "exhausted" status of antioxidant defense system triggering development of metabolic syndrome and chronic inflammation. Green perilla (Perilla frutescens) is commonly used in Asian cuisines and traditional medicine in southeast Asia. Green perilla possesses numerous beneficial effects including anti-inflammatory and antioxidant functions. To investigate the potentials of green perilla leaf extract (PE) on oxidative stress, we induced oxidative stress by high-fat diet (HFD) in aging mice. MATERIALS/METHODS: C57BL/6J male mice were fed HFD continuously for 53 weeks. Then, mice were divided into three groups for 12 weeks: a normal diet fed reference group (NDcon), high-fat diet fed group (HDcon), and high-fat diet PE treated group (HDPE, 400 mg/kg of body weight). Biochemical analyses of serum and liver tissues were performed to assess metabolic and inflammatory damage and oxidative status. Hepatic gene expression of oxidative stress and inflammation related enzymes were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: PE improved hepatopathology. PE also improved the lipid profiles and antioxidant enzymes, including hepatic glutathione peroxidase (GPx) and superoxide dismutase (SOD) and catalase (CAT) in serum and liver. Hepatic gene expressions of antioxidant and anti-inflammatory related enzymes, such as SOD-1, CAT, interleukin 4 (IL-4) and nuclear factor erythroid 2-related factor (Nrf2) were significantly enhanced by PE. PE also reduced the levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) in the serum and liver; moreover, PE suppressed hepatic gene expression involved in pro-inflammatory response; Cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CONCLUSIONS: This research opens opportunities for further investigations of PE as a functional food and possible anti-aging agent due to its attenuative effects against oxidative stress, resulting from HFD and aging in the future.

• Journal of Microbiology and Biotechnology
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• v.28 no.8
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• pp.1270-1281
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• 2018

Periodontal disease is triggered by the host immune response to pathogens in the microbial biofilm. Worsening of periodontal disease destroys the tooth-supporting tissues and alveolar bone. As oral inflammation can induce systemic diseases in humans, it is important to prevent periodontal disease. In this study, we demonstrated that Curcuma xanthorrhiza supercritical extract (CXS) and its active compound, xanthorrhizol (XAN), exhibit anti-inflammatory effects on lipopolysaccharide (LPS)-treated human gingival fibroblast-1 cells and anti-osteoclastic effects on receptor activator of nuclear factor kappa B ligand (RANKL)-treated RAW264.7 cells. LPS-upregulated inflammatory factors, such as nuclear factor kappa B p65 and $interleukin-1{\beta}$, were prominently reduced by CXS and XAN. In addition, RANKL-induced osteoclastic factors, such as nuclear factor of activated T-cells c1, tartrate-resistant acid phosphatase, and cathepsin K, were decreased in the presence of CXS and XAN. CXS and XAN inhibited the mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathway. Collectively, these results provide evidence that CXS and XAN suppress LPS-induced inflammation and RANKL-induced osteoclastogenesis by suppressing the MAPK/AP-1 pathway.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.327-332
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• 2019

Alzheimer's disease (AD) is a common neurodegenerative disease. Oxidative stress by amyloid beta peptide (Aβ) of neuronal cell is the most cause of AD. In the present study, protective effects of several flavonoids such as kaempferol (K), kaempferol-3-O-glucoside (KG), quercetin (Q) and quercetin-3-β-ᴅ-glucoside (QG) from Aβ_25-35 were investigated using C6 glial cell. Treatment of Aβ_25-35 to C6 glial cell showed decrease of cell viability, while treatment of flavonoids such as Q and QG increased cell viability. In addition, treatment of flavonoids declined reactive oxygen species (ROS) production compared with Aβ_25-35-induced control. The ROS production was increased by treatment of Aβ_25-35 to 133.39%, while KG and QG at concentration of 1 μM decreased ROS production to 107.44 and 113.10%, respectively. To study mechanisms of protective effect of these flavonoids against Aβ_25-35, the protein expression related to inflammation under Aβ_25-35-induced C6 glial cell was investigated. The results showed that C6 glial cell under Aβ_25-35-induced oxidative stress up-regulated inflammation-related protein expressions. However, treatment of flavonoids led to reduction of protein expression such as inducible nitric oxide synthase, cyclooxygenase-2 and interleukin-1β. Especially, treatment of KG and QG decreased more effectively inflammation-related protein expression than its aglycones, K and Q. Therefore, the present results indicated that K, Q and its glycosides attenuated Aβ_25-35-induced neuronal oxidative stress and inflammation.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.338-349
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• 1999

Polymorphonuclear leukocytes(PMN) are the predominant inflammatory cells recruited in acute lung injury such as adult respiratory distress syndrome, pneumonia and also chronic lung disease such as idiopathic pulmonary fibrosis and pulmonary emphysema. Interleukin-8(IL-8) is an 8,000 D protein produced by many cells and has potent neutrophil chemoattractant and activating properties. The GRO, also called melanoma growth-stimulatory activity(MGSA), referring to a peptide of 73 amino acids, was reported to be mitogenic for cultured human melanoma cells. Mature GRO/MGSA has marked sequence similarity to IL-8. In view of the structural similarities to IL-8, it was of particular interest to test GRO for neutrophil activating and chemotactic properties. We found a significant release of IL-8 and GRO/MGSA from the cultured human umbilical vein endothelial cell(HUVEC) which was stimulated either with TNF$\alpha$ or IL-1$\beta$ and also found the expression of IL-8 and GRO/MGSA mRNA. Neutrophil chemotactic activity was enhanced in accordance with the increased IL-8 and GRO/MGSA. Our study also suggest that the IL-8 is more important in the increased neutrophil chemotactic activity than GRO/MGSA when endothelial cell is stimulated with TNF$\alpha$ or IL-1$\beta$ in vitro.