• The Korea Journal of Herbology
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• v.23 no.3
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• pp.73-83
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• 2008

Objectives : The root of Zingiber officinale ROSC. (Zingiberis Rhizoma Recens; Ginger) has been widely used as one of folk remedies and food materials in many traditional preparations. Ginger is known as an effective appetite enhancer and anti-inflammatory agent. This study was performed to investigate the effect of ginger chloroform fraction (GCF) in microglia which play a central role on brain inflammation in neurodegenerative diseases. Methods : Dried ginger was extracted with 80% methanol, and then fractionated with chloroform. BV2 mouse microglial cells were cultured with different concentrations of GCF and then stimulated with LPS (1 ${\mu}g/m{\ell}$) at indicated times. The cell toxicity of GCF was determined by MTT assay. The concentrations of NO, PGE2 and cytokines were measured by Griess assay and enzyme-linked immunosorbant assay. The mRNA and protein expressions of iNOS, COX-2 and cytokines were determined by RT-PCR and Western blotting. The phosphorylation of three MAPKs (p38 MAPK, ERK1/2 and JNK) and $NF-{\kappa}B$ activation were determined by Western blotting. Results : GCF significantly inhibited LPS-induced production of inflammatory mediators, NO, $PGE_2$ and proinflammatory cytokines ($TNF-{\alpha}$ and $IL-1{\beta}$) in a dose-dependent manner. GCF attenuated LPS-induced expression of mRNA and protein of inflammatory enzymes, iNOS, COX-2 and proinflammatory cytokines through suppressing the phosphorylation of ERK1/2 and p38 MAPK and the activation of p65 $NF-{\kappa}B$ in BV2 cells. Conclusions : This study suggests that GCF may have an anti-inflammatory property through suppressing the inflammatory mediator production released by activated microglia after the brain injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.2
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• pp.227-233
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• 2011

Water Fermented and Ethanol Fermented Extracts from Rhei Radix et Rhizoma exhibit potent anti-inflammatory activity with an unknown mechanism. To elucidate the molecular mechanisms of W-FR and E-FR on pharmacological and biochemical actions in inflammation, we examined the effect of W-FR and E-FR on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. The investigation focused on whether FR inhibited nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6) and the expressions of iNOS, COX-2 in LPS-stimulated RAW 264.7 cells. We found that FR inhibited LPS-induced NO, TNF-${\alpha}$ and IL-6 productions as well as the expressions of iNOS and COX-2. These results suggest that W-FR and E-FR have inhibitory effects on LPS-induced TNF-${\alpha}$, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage.

• Molecules and Cells
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• v.23 no.3
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• pp.398-404
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• 2007

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in various pathophysiological processes such as inflammation and carcinogenesis. In a search for inhibitors of COX-2 and iNOS production we found that extracts of Stewartia koreana strongly inhibited NO and $PGE_2$ production in LPS-treated macrophage RAW 264.7 cells. We have now shown that the mRNA and protein levels of iNOS and COX-2 are reduced by the Stewartia koreana extract (SKE). SKE inhibited expression of an NF-${\kappa}B$ reporter gene in response to LPS, and gel mobility shift assays revealed that SKE reduced NF-${\kappa}B$ DNA-binding activity. The extract also inhibited LPS-induced phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Administration of the extract reduced the symptoms of arthritis in a collagen-induced arthritic mouse model. These results indicate that Stewartia extracts contain potentially useful agents for preventing and treating inflammatory diseases.

• Journal of Life Science
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• v.24 no.5
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• pp.476-484
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• 2014

Obesity, which is characterized by a state of mild chronic inflammation, is known to cause metabolic diseases. This study was carried out to investigate the effect of lyophilized dropwort vinegar powder (DVP) on adipocyte differentiation and inflammation in T3-L1 preadipocyte and RAW 264.7 macrophage cell lines. DVP inhibited the differentiation of 3T3-L1 preadipocytes induced by a mixture of IBMX, dexamethasone, and insulin (MDI). Western blot analysis of cell lysates showed that DVP decreased the levels of two major transcription factors involved in adipogenesis, peroxisome proliferator- activated receptor-${\gamma}$ (PPAR-${\gamma}$) and CCAAT-enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$). DVP also significantly suppressed lipopolysaccharide (LPS)-induced production of nitric oxide (NO), and this was accompanied by a decrease in inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. These results demonstrate that DVP inhibits MDI-induced adipocyte differentiation of 3T3-L1 cells and LPS-induced inflammation in RAW 264.7 macrophage cells. The findings indicate that this natural product may be a good candidate as to prevent metabolic diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.37-42
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• 2006

Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants such as lipopolysaccharide (LPS) leads to the production of significant amounts of MMP-9. Here, we show that LPS-induced MMP-9 production and activation was inhibited by the water extract from the fruit of Chaenomeles sinensis (CS), the root of Polygonum cuspidatum (PC), but increased by the extract from Boswellia carterii (BC). To investigate the mechanism by which those extracts inhibits MMP-9 activation, we examined the level of MMP-9 mRNA expression. We observed a significant change in the MMP-9 expression between LPS alone and LPS plus Chaenomeles sinensis and Polygonum cuspidatum extracts-treated cells. In addition, LPS significantly up-regulated MMP-9 promoter activity in Raw 264.7 cells, which was attenuated by the CS and PS extracts. However, water extracts from Boswellia carterii increased MMP-9 expression and MMP-9 promoter activity which were induced by LPS treatment in Raw 264.7 cells. These data suggest that water extracts from Chaenomeles sinensis and Polygonum cuspidatum can modulate anti-inflammatory immune response, which may be in part associated with the regulation of MMP-9 production and/or activation through the regulation of MMP-9 expression in mouse macrophage cells.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.12
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• pp.1784-1795
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• 2017

Objective: The study examined the effect of intravenous administration of bacterial endotoxin-lipopolysaccharide (LPS) -on the nocturnal secretion of melatonin and on the expression of enzymes of the melatonin biosynthetic pathway in the pineal gland of ewes, taking into account two different photoperiodic conditions: short-night (SN; n = 12) and long-night (LN; n = 12). Methods: In both experiments, animals (n = 12) were randomly divided into two groups: control (n = 6) and LPS-treated (n = 6) one. Two hours after sunset, animals received an injection of LPS or saline. Blood samples were collected starting one hour after sunset and continuing for 3 hours after the treatment. The ewes were euthanized 3 hours after LPS/saline treatment. The concentration of hormones in plasma was assayed by radioimmunoassay. In the pineal gland, the content of serotonin and its metabolite was determined by HPLC; whereas the expression of examined genes and protein was assayed using real-time polymerase chain reaction and Western Blot, respectively. Results: Endotoxin administration lowered (p<0.05) levels of circulating melatonin in animals from LN photoperiod only during the first hour after treatment, while in ewes from SN photoperiod only in the third hour after the injection. Inflammation more substantially suppressed biosynthesis of melatonin in ewes from SN photoperiod, which were also characterised by lower (p<0.05) cortisol concentrations after LPS treatment compared with animals from LN photoperiod. In the pineal gland of ewes subjected to SN photoperiod, LPS reduced (p<0.05) serotonin content and the expression of melatonin biosynthetic pathway enzymes, such as tryptophan hydroxylase and arylalkylamine-N-acetyltransferase. Pineal activity may be disturbed by circulating LPS and proinflammatory cytokines because the expression of mRNAs encoding their corresponding receptors was determined in this gland. Conclusion: The present study showed that peripheral inflammation reduces the secretion of melatonin, but this effect may be influenced by the photoperiod.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.156-166
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• 2022

Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescencelabeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/ MD2 complex and GRo (K_D value of 1.16 × 10^-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.6
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• pp.1032-1038
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• 2011

Yeonguemjiri-tang(連芩止痢湯, YGT) exhibits potent anti-inflammatory activity in widely intestine disease, but its mechanism undisclosed. To elucidate the molecular mechanisms of YGT on pharmacological and biochemical actions in inflammation, we examined the effect of YGT on pro-inflammatory mediators in phorbol 12-myristate 13-acetate (PMA) plus A23187-induced mast cell and lipopolysaccharide (LPS)-stimulated macrophages. The investigation focused on whether YGT inhibited pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in PMA plus A23187-induced HMC-1 cells and inflammatory madiators such as nitric oxide (NO), TNF-${\alpha}$, IL-6, iNOS, COX-2 in LPS-stimulated RAW 264.7 cells. We found that YGT inhibited LPS-induced NO, TNF-${\alpha}$ and IL-6 productions as well as the expressions of iNOS and COX-2. These results suggest that YGT has inhibitory effects on mast cell-mediated and macrophage-mediated inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.2
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• pp.99-105
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• 2018

The aim of this study is to compare the anti-inflammatory and immunological activity of different parts (bone, meat, and rind) of Yeonsan Ogye (YO). In order to evaluate cytotoxicity, MTT assay was performed. We investigated the production of nitric oxide (NO) and pro-inflammatory cytokines, such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$, in LPS-induced RAW264.7 cells. All parts of the YO showed no toxicity at concentrations of 1, 10, and $100{\mu}g/m{\ell}$. Rooster's bone, hen's bone, and rind decreased the production of NO. And rooster's bone, meat, and hen's bone also attenuated TNF-${\alpha}$ production in LPS-induced RAW 264.7 cells. In addition, all parts of the YO decreased IL-$1{\beta}$ and IL-6 production in LPS-induced RAW264.7 cells, whereas they all increased IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ production in normal RAW264.7 cells. Rooster exhibited higher immune activation and inhibitory activity on inflammation than a hen, and among different parts of the YO, bone showed the highest activity. Our results demonstrated and compared the anti-inflammatory and immunological activity of different parts of the YO. These results suggest that YO may be developed as a raw material for new health supplement food and medicine to attenuate various symptoms related to inflammation and immunity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.503-509
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• 2011

Jakyaktang(芍藥湯; JYT) exhibits potent anti-inflammatory activity in widely intestinal disease, but its mechanism was undisclosed. To elucidate the molecular mechanisms of JYT on pharmacological and biochemical actions in inflammation, we examined the effect of JYT on pro-inflammatory mediators in phorbol 12-myristate 13-acetate (PMA) plus A23187-induced mast cell and lipopolysaccharide (LPS)-stimulated macrophages. The investigation focused on whether JYT inhibited pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in PMA plus A23187- induced HMC-1 cells and inflammatory madiators such as nitric oxide (NO), TNF-${\alpha}$, IL-6, iNOS, COX-2 in LPS-stimulated RAW 264.7 cells. We found that JYT inhibited LPS-induced NO, TNF-${\alpha}$ and IL-6 productions as well as the expressions of iNOS and COX-2. These results suggest that JYT has inhibitory effects on mast cell-mediated and macropage-mediated inflammation.