• BMB Reports
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• v.43 no.9
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• pp.629-634
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• 2010

Endotoxin including lipopolysaccharide (LPS) confers organ tolerance against subsequent challenge by ischemia and reperfusion (I/R) insult. The mechanisms underlying this powerful adaptive defense remain to be defined. Therefore, in this study we attempted to determine whether nitric oxide (NO) and its associated enzymes, inducible NOS (iNOS) and endothelial NOS (eNOS, a constitutive NOS), are associated with LPS-induced renal tolerance against I/R injury, using iNOS (iNOS knock-out) or eNOS (eNOS knock-out) gene-deleted mice. A systemic low dose of LPS pretreatment protected kidney against I/R injury. LPS treatment increased the activity and expression of iNOS, but not eNOS, in kidney tissue. LPS pretreatment in iNOS, but not eNOS, knock-out mice did not protect kidney against I/R injury. In conclusion, the kidney tolerance to I/R injury conferred by pretreatment with LPS is mediated by increased expression and activation of iNOS.

• Journal of Periodontal and Implant Science
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• v.38 no.3
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• pp.511-520
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• 2008

Purpose: Diabetes mellitus is a clinically and genetically heterogeneous group of metabolic disorders manifested by abnormally high levels of glucose in the blood. Mounting evidence demonstrates that diabetes is a risk factor for gingivitis and periodontitis. The circulating mononuclear phagocytes in diabetic patients with hyperglycemia are chronically exposed to high level of serum glucose. Thus, this study attempted to determine the effect of pre-exposure of monocytes and macrophages to high concentration of glucose on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators. Material and Methods: For this purpose, cells were cultured in medium containing normal (5 mM) or high glucose (25 mM) for 4-5 weeks before treatment for 24 h with LPS. LPS was highly purified from Porphyromonas gingivalis or Prevotella intermedia by phenol extraction. Result: Results showed that prolonged pre-exposure of cells to high glucose markedly increased LPS-stimulated NO secretion when compared to normal glucose. In addition to NO, high glucose also augmented LPS-stimulated IL-6, IL-8, and TNF-$\alpha$ secretion after cells were exposed to high glucose for 4 weeks. Conclusion: The present study demonstrates that pre-exposure of mononuclear phagocytes with high glucose augments LPS-stimulated production of pro-inflammatory mediators. These findings may explain why periodontal tissue destruction in diabetic patients is more severe than that in non-diabetic individuals.

• Korean Journal of Acupuncture
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• v.26 no.2
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• pp.127-143
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• 2009

Objective : This study aimed to evaluate the effects of Plantaginis Semen herbal-acupuncture (PS-HA) at KI10 (Umgok) on nephritis induced by lipopolysaccharide (LPS) in rat. Methods : The authors performed several experimental items including measurements of urinary volume, WBC in blood, BUN, creatine, TNF-$\alpha$, CINC-1 in serum, creatinine, total protein in urine, TNF-$\alpha$, MPO in kidney and histological analysis of renal tissue. Results : PS-HA at KI10 significantly reduced WBC in blood, BUN, TNF-$\alpha$ in serum of LPS-stimulated rats. PS-HA at KI10 significantly increased urinary volume in LPS-stimulated rats. And PS-HA at KI10 significantly reduced MPO in kidney of LPS-stimulated rats. Conclusion : Taken together, PS-HA at KI10 has a therapeutic effect on nephritis in LPS-stimulated rat. Therefore, it is suggested that PS-HA at KI10 may be an useful therapeutics for nephritis in clinical field.

• The Journal of Korean Medicine
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• v.43 no.1
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• pp.99-111
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• 2022

Objectives: Rehmanniae Radix Preparata (RRP) has been used as a traditional remedy to treat gynecology and endocrine diseases. Recently, studies on antioxidant and anti-inflammatory effects of RRP have been reported, so it was judged that RRP extracts would have an anti-depressive effect. Methods: We investigated the anti-neuroinflammatory and anti-depressive effect of RRP on lipopolysaccharide (LPS)-induced depression and LPS-stimulated BV2 microglia. RRP inhibited the LPS-stimulated excessive release of nitrite in the BV2 cells. RRP also significantly inhibited the inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in LPS-stimulated BV2 microglial cells. Results: RRP significantly suppressed the LPS-induced mitogen-activated protein kinase (MAPKs) and nuclear factor (NF)-𝜅B activation. In addition, administration of RRP not only inhibited the immobility time in the forced swimming test (FST) but also increased the total travel distance in the open field test (OFT). Also, RRP inhibited the elevation of TNF-alpha, IL-1beta, and IL-6 in brain of LPS-injected mice. Conclusions: Considering the overall results, our study showed that RRP exhibited the anti-neuroinflammatory and anti-depressive activities via deactivation of MAPKs and NF-𝜅B.

• Journal of Acupuncture Research
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• v.18 no.1
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• pp.113-128
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• 2001

Objective : To investigate the effect of BUM aqua-acupuncture in treating the RA, the immunosis to logical analysis of LPS induced arthritis in mice to study this. For 14th day after the injection of LPS & BUM injection, the distribution of fibroblast, collagen, CD54(ICAM-1), CD106(VCAM-1), IL-$1{\beta}$, IL-2 receptor, CDl lb(macrophage) were examined on synovial capsule of mice knee joint. For 14th day after the injection of LPS & BUM injection, the distribucion of CD4(TH cell), CD8(TC cell), CD40(B cell) were examined on common iliac lymph node in mice. Methods : The experimental model of arthritis was induced by injection of 300${\mu}g$/kg LPS in BALB/c mice weighing 30g. The 100${\mu}l$ BUM aqua-acupuncture which compounded calculus bovis, fel ursi and moschus was injected into GB34 of mice every other day for 12 days. For 3rd, 7th, 14th day after the injection of LPS, the neutrophil, lymphocyte and monocytc counts in WBC were measured using hemacytometer. Results : The obstain results are summarized as follows ; 1. In sample group, the neutrophils counts were increased and the lympnocytes counts were decreased compared with control group. 2. The distribution of fibrosis & fibroblast on synovial membrane were decreased compared with control group. 3. The distribution of collagen fiber on synovial membrane were decreased compared' with control group. 4. The distribution of CD54(ICAM-1) & CD106(VCAM-1) on synovial membrane were decreased compared with control group. 5. The distribution of IL-$1{\beta}$ & IL-2 receptor on synovial membrane were decreased compared with control group. 6. The distribution of CDb(macrophage) on synovial membrane were decreased compared with control group. 7. The distribution of CD4(TH cell), CD8(TC cell) and CD40(B cell) in common iliac lymph nodes were decreased compared with control group. Conclusions : BUM aqua-acupuncture stimulation decreased inflammatory responses LPS induced arthritis in mice.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.70-78
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• 2009

Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

• Biomedical Science Letters
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• v.21 no.4
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• pp.218-226
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• 2015

The present study investigated the mechanisms of licochalcone B (LicB)-mediated inhibition of the inflammatory response in murine macrophages. RAW264.7 murine macrophages were cultured in the absence or presence of lipopolysacharide (LPS) with LicB. LicB suppressed the generation of nitric oxide and the pro-inflammatory cytokines interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor-${\alpha}$. LicB also inhibited the expression of mRNA for inducible nitric oxide synthase and pro-inflammatory cytokines induced by LPS. Moreover, LicB inhibited nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 translocation into the nucleus in a dose-dependent manner. Thus, LicB mainly exerts its anti-inflammatory effects by inhibiting the LPS-induced NF-${\kappa}B$ and activator protein-1 signaling pathways in macrophages, which subsequently diminishes the expression and release of various inflammatory mediators. LicB shows promise as a therapeutic agent in inflammatory diseases.

• Journal of Evidence-Based Herbal Medicine
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• v.2 no.1
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• pp.1-5
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• 2009

Objectives : The purpose of this study was to investigate the anti-inflammatory effects of Ecklonia cava butanol extract (BFEC) on RAW 264.7 cells. Method : To evaluate of anti-inflammatory of BFEC, We examined cytokine and Nitric oxide(NO) production in lipopolysacchride (LPS)-induced RAW 264.7 cell. Result : Extract of BFEC inhibit LPS-induced interleukin (IL)-6, NO production in human monocyte RAW 264.7 cells. Conclusion : BFEC down-regulated LPS-induced IL-6, NO production, which may be provide a clinical basis for anti-inflammatory properities of BFEC.

• Toxicological Research
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• v.23 no.1
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• pp.19-24
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• 2007

We demonstrate that paclitaxel, an antitumor agent derived from yew tree, inhibits LPS- and $IFN-{\gamma}$-induced NF-kB/Rel activation in RAW 264.7 cells. Previously, paclitaxel ($>10{\mu}M$) has been known to induce iNOS gene expression in macrophages. However, in the previous report we described that the pretreatment of macrophages with low concentration of paclitaxel ($0.1{\mu}M$) for 8 h inhibited LPS-induced iNOS gene expression. Pretreatment of RAW 264.7 cells with paclitaxel significantly inhibited NF-kB/Rel transcriptional activation. Electrophoretic mobility shift assay further confirmed that pretreatment of macrophages with paclitaxel inhibited NF-kB/Rel DNA binding. Taxotere, a semisynthetic analog of paclitaxel, also inhibited LPS- and $IFN-{\gamma}$-induced iNOS gene expression. Collectively, these series of experiments indicate that paclitaxel inhibits iNOS gene expression by blocking NF-kB/Rel activation.

• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.100-107
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• 1999

Apoptosis is now widely recognized as a common form of cell death and represents mechanism of cell clearance in many physiological situations where deletion of cells is required. In vivo administration of bacterial lipopolysaccharide (LPS) to Balb/c mice induced DNA fragmentation in the thymus. DNA fragmentation in the thymus was roughly dependent on the dose of LPS injected and reached the peak 18 hours after injection. This apoptosis in the thymus might be mediated due to LPS stimulant. DEN (diethylnitrosamine) has been shown to cause liver cancer in experimental animals and humans. The hepatic tumorigenesis was induced by ad libitum feeding of DEN only. It was suggested that DEN induced hepatic tumorgenesis in rat is a good reproducible model for studying biochemical and pathophysiological changes associated with the development of hepatic tumorigenesis and apoptosis.