• 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.

• The Journal of the Korean Society for Microbiology
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• v.35 no.1
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• pp.9-18
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• 2000

Immunological mechanisms involving the release of inflammatory factors by HIV-1 infected microglia in the brain have been implicated in the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix metalloproteinases (MMPs) activity can be influenced by variety of inflammatory mediators, this study was undertaken to look for a correlation between the MMP-9 release and the production of TNF-${\alpha}$ in response to HIV-1 p24 in the human monocyte cell line THP-1 as a model for microglia. First, it was shown that HIV-l core p24 antigen induced THP-1 to secrete MMP-9 in a dose response manner while it elicited a little effect on MMP-2 release in human astroglial cell line T98G. Next, it was found that p24 induced THP-1 to secrete TNF-${\alpha}$ without prior differentiation into macrophages by phorbol myristate acetate (PMA) treatment. Furthermore, anti-TNF-${\alpha}$ neutralizing antibodies significantly blocked p24-induced MMP-9 release in a dose dependent manner. Our data indicate that p24 antigen induces monocytic MMP-9 release by triggering up-regulation of TNF-${\alpha}$ secretion.

• Herbal Formula Science
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• v.11 no.1
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• pp.115-128
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• 2003

Bojungikgitang is the water extracts prepared from Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Astractylodis Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Bupleuri Radix, Cimicifugae Rhizoma, which has been used for the treatment of indigestion, and immunological disease in oriental countries. In this study, the effects of Bojungikgitang on the productions of nitiric oxide (NO) and prostaglandin $E_2\;(PGE_2)$, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using RAW 264.7 macrophages activated with $interferon-{\gamma}\;(IFN-{\gamma})$ plus lipopolysaccharide (LPS). Bojungikgitang (10-400 ${\mu}$g/ml) per se had no cytotoxic effect in unstimulated macrophages, but this compound dose-dependently reduced the release of NO and $PGE_2$ caused by stimulation of $LPS/IFN-{\gamma}$. The levels of iNOS and COX-2 protein were markedly suppressed by the treatment with Bojungikgitang in a concentration dependent manner. Moreover, Bojungikgitang also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (1L)-1${\beta}$ and IL-6 in LPS-stimulated RAW 264.7 macrophages. These results suggest that Bojungikgitang decreases the NO and $PGE_2$ production in macrophages by inhibiting iNOS and COX-2 expression and these properties may contribute to the anti-inflammatory activity of Bojungikgitang.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.91-101
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• 2008

Objectives: In this study, we investigated the inhibitory effects of Ampelopsis Radix methanol(AR-M) extract on allergic inflammation in activated human mast cells and its potential therapeutic or toxic effects. Methods: Ampelopsis Radix(AR) was extracted with 80% methanol. HMC-1 cells, a human mast cell line, were treated with different concentrations of AR-M extract, and then stimulated with PMA plus A23187. The cell toxicity of AR-M extract was determined by MTT assay. The concentrations of $PGE_2$ and cytokines were measured by ELISA. The gene expression of COX-2 and its protein levels were determined by RT-PCR and Western blot. The phosphorylation of ERK MAPK and the NF-${\kappa}B$ activation were determined by Western blot. Results: AR-M extract was significantly inhibited the production of PGE2 and inflammatory cytokines(TNF-${\alpha}$, IL-6 and IL-8) in PMA/A23187-stimulated HMC-1 cells. AR-M extract also attenuated the mRNA expression of COX-2 and its protein induction. Furthermore, AR-M extract attenuated PMA/A23187-induced phophorylation of ERK1/2 MAPK and the NF-${\kappa}B$ p65 subunit translocation into nuclear of HMC-1 cells. AR-M extract significantly decreased PMN A23187-induced release of histamine in a dose-dependent manner. Conclusions: These results indicate that Ampelopsis Radix shows the property of anti-allergic inflammation In vitro through suppressing the production of inflammatory mediators released from mast cells, suggesting have a potential for the treatment of allergic diseases.

• BMB Reports
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• v.43 no.1
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• pp.46-51
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• 2010

Thermal burn injury induces inflammatory cell infiltrates in the dermis and thickening of the epidermis. Following a burn injury, various mediators, including reactive oxygen species (ROS), are produced in macrophages and neutrophils, exposing all tissues to oxidative injury. The anti-oxidant activities of flavonoids have been widely exploited to scavenge ROS. In this study, we observed that several flavonoids-kaempferol, quercetin, fisetin, and chrysin-inhibit LPS-induced IL-8 promoter activation in RAW 264.7 cells. In contrast with quercetin and fisetin, pretreatment of kaempferol and chrysin did not decrease cell viability. Inflammatory cell infiltrates in the dermis and thickening of the epidermis induced by burn injuries in mice was relieved by kaempferol treatment. However, the injury was worsened by fisetin, quercetin, and chrysin. Expression of TNF-a induced by burn injuries was decreased by kaempferol. These findings suggest the potential use of kaempferol as a therapeutic in thermal burn-induced skin injuries.

• Korean Journal of Pharmacognosy
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• v.43 no.3
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• pp.217-223
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• 2012

In the present study, we investigated anti-inflammatory activity of artemisinic acid in HaCaT cells and RAW264.7 cells. Artemisinic acid showed inhibitory activity on macrophage-derived chemokines (MDC) expression, a factor related with atopic dermatitis (AD), in interferon (IFN)-${\gamma}$ and tumor necrosis factor (TNF)-${\alpha}$-stimulated HaCaT cells. In the study on action mechanism, pretreated artemisinic acid reduced the phosphorylation of STAT1 and p38 and the degradation of $I{\kappa}B$ by IFN-${\gamma}$ and TNF-${\alpha}$ stimulations. However, artemisinic acid didn't show the inhibitory activity on LPS-induced inflammatory mediators (NO, $PGE_2$, IL-6) in RAW264.7 cell. These results indicate that artemisinic acid inhibits IFN-${\gamma}$ and TNF-${\alpha}$-induced MDC expression through inhibition of signal factors, STAT1, NF-${\kappa}B$, and p38, in HaCaT keratinocytes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.779-784
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• 2005

Mast cells are a potent source of mediators that regulate the inflammatory response in allergic reaction. To evaluate the atopic allergic effect of Asiasari radix(AR), the author investigated a possible effect of AR on mast cell-mediated allergic reaction, cytokines secretion and mRNA expression in vivo and in vitro. In mice orally administered by AR (0.01, 0.1 and 1.0 g/kg) for 1 h, compound 48/80-induced ear swelling was significantly reduced (P < 0.05). AR had inhibitory effects on tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-8, and IL-6 secretion from HMC-1. Significant reduced levels of $TNF-{\alpha}$ mRNA was observed in the human mast cell line (HMC-1) with AR (1.0 mg/ml). In addition, AR had no cytotoxic effect on cell viability. These results suggest that AR contributes to the treatment of atopic allergic reactions, and that its action may be due to inhibition of cytokine secretion and mRNA expression in HMC-1.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.193-199
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• 2014

The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin $D_2$ ($PGD_2$), leukotriene $C_4$ ($LTC_4$), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of $PGD_2$ and $LTC_4$ in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun $NH_2$-terminal kinase and p38), and the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.593-602
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• 2020

Background: Heat stress orchestrates neurodegenerative disorders and results in the formation of reactive oxygen species that leads to cell death. Although the immunomodulatory effects of ginseng are well studied, the mechanism by which ginseng alleviates heat stress in the brain remains elusive. Methods: Rats were exposed to intermittent heat stress for 6 months, and brain samples were examined to elucidate survival and antiinflammatory effect after Korean Red Ginseng (KRG) treatment. Results: Intermittent long-term heat stress (ILTHS) upregulated the expression of cyclooxygenase 2 and inducible nitric oxide synthase, increasing infiltration of inflammatory cells (hematoxylin and eosin staining) and the level of proinflammatory cytokines [tumor necrosis factor α, interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6], leading to cell death (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) and elevated markers of oxidative stress damage (myeloperoxidase and malondialdehyde), resulting in the downregulation of antiapoptotic markers (Bcl-2 and Bcl-x_L) and expression of estrogen receptor beta and brain-derived neurotrophic factor, key factors in regulating neuronal cell survival. In contrast, KRG mitigated ILTHS-induced release of proinflammatory mediators, upregulated the mRNA level of the antiinflammatory cytokine IL-10, and increased myeloperoxidase and malondialdehyde levels. In addition, KRG significantly decreased the expression of the proapoptotic marker (Bax), did not affect caspase-3 expression, but increased the expression of antiapoptotic markers (Bcl-2 and Bcl-x_L). Furthermore, KRG significantly activated the expression of both estrogen receptor beta and brain-derived neurotrophic factor. Conclusion: ILTHS induced oxidative stress responses and inflammatory molecules, which can lead to impaired neurogenesis and ultimately neuronal death, whereas, KRG, being the antioxidant, inhibited neuronal damage and increased cell viability.