• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.89-89
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• 2018

Abeliophyllum distichum is a medicinal plant used in regional traditional medicine to relieve pain in inflammatory processes. In this study, anti-inflammatory effects of Abeliophyllum distichum stem (ADS) ethyl acetate extract were examined. Furthermore, possible molecular mechanisms of the anti-inflammatory effects were dissected. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced pro-inflammatory cytokine production in murine macrophage-like cell line Raw264.7 cells and human microglial cell line BV2 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK, and MAPK, and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 were investigated by Western blot analysis. The extract of ADS significantly decreased the production of pro-inflammatory cytokines. In addition, the extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. Our findings provide evidence for the popular use of Abeliophylli distichum in inflammation around Goesan region and also suggest that the stem extract has potential therapeutic benefits against several inflammatory diseases.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.90-90
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• 2018

Kochiae Fructus is a medicinal plant used as medicine of the urinary organs, skin disease and inflammation. In this study, anti-inflammatory activity of Kochiae Fructus extract and its possible mechanisms of action were examined. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO), pro-inflammatory cytokine production and matrix metalloprotease-9 (MMP-9) in murine macrophage-like cell line Raw 264.7 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK and MAPK and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 were investigated by Wesern blot analysis. The extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. As a result, we suggest that the extract of Kochiae Fructus decreased the production of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6), nitric oxide, MMP-9 in LPS-induced Raw264.7 cells. Kochiae Fructus has possibility to be used as therapeutic benefits against inflammatory diseases.

• Molecules and Cells
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• v.37 no.12
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• pp.899-906
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• 2014

Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

• BMB Reports
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• v.52 no.6
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• pp.409-414
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• 2019

Natural compounds isolated from medicinal herbs and plants have immense significance in maintaining bone health. Hydrolysable tannins have been shown to possess a variety of medicinal properties including antiviral, anticancer, and anti-osteoclastogenic activities. As a part of a study on the discovery of alternative agent against skeletal diseases, we isolated a hydrolysable tannin, 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-${\beta}$-D-glucose (DTOGG), from Galla Rhois and examined the effect on osteoclast formation and function. We found that DTOGG significantly inhibited receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation by downregulating the expression of the key regulator in osteoclastogenesis as well as osteoclast-related genes. Analysis of RANKL/RANK signaling revealed that DTOGG impaired activation of $I{\kappa}B{\alpha}$ and p65 in the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-${\kappa}B$) signaling pathway. Furthermore, DTOGG reduced bone resorbing activity of osteoclasts, compared to the vehicle-treated control. These results suggest that DTOGG could be a useful natural compound to manage osteoclast-mediated skeletal diseases.

• The Journal of Pediatrics of Korean Medicine
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• v.25 no.1
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• pp.28-39
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• 2011

Objectives: SaengRyoSaMulTang is a herbal formula in Oriental Medicine, known anti-allergens. However, its mechanism and cellular targets have not been found yet. Thus the study has developed to investigate the suppressive effect of SaengRyoSaMulTang. Methods: In the study, cellular viability, IL-4, IL-13 mRNA expression, IL-4, IL-13 production, manifestations of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-${\kappa}$B p65 transcription factors were examined by Real-Time PCR, ELISA analysis and western blotting. Results: As a result of treating with SaengRyoSaMulTang extract(SRSMT), the study has shown that the amount of Th2 cytokines, which include PI induced IL-4 and IL-13, plays a significant role in suppressing effect. RBL-2H3 mast cells significantly suppressed the PI-induced Th2 cytokine production including IL-4 and IL-13 in a dose dependent manner. PI-induced IL-4 and IL-13 production was significantly suppressed by SRSMT intervention. Western blot analysis of transcription factors involving IL-4 and IL-13 expression also revealed a prominent decreases of mast cell's specific transcription factors including GATA-1, GATA-2, NF-AT2, c-Jun and c-Fos, but NF-${\kappa}$B p65. Conclusions: The study suggests that the anti-allergenic activities of SRSMT may regulate the transcription factors GATA-1, GATA-2, NF-AT2, c-Jun and c-Fos inhibiting Th2 cytokines IL-4 and IL-13 in mast cells.

• Herbal Formula Science
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• v.22 no.1
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• pp.79-92
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• 2014

Objectives : The aim of this study was identification of the anti-oxidative and anti-inflammatory effects of Talmyung-san (TMS) in mouse macrophage, RAW264.7 cells. Methods : To identify the anti-oxidative effect of TMS, scavenging activities of DPPH radical, nitric oxide and peroxynitrite were measured in vitro. In RAW264.7 cells, DCFH-DA assay was conducted to examine the inhibitory effect of TMS on ROS production in response to lipopolysaccharide. And the productions of nitric oxide (NO), $PGE_2$ and pro-inflammatory cytokines were measured. The levels of COX-2, iNOS, nuclear NF-${\kappa}B$ p65 expression and phosphorylation of $I{\kappa}B-{\alpha}$ in cytosol were detected by western blotting analyses. Results : TMS couldn't scavenged DPPH radical, but nitric oxide and peroxynitrite were decreased. TMS decreased intracellular ROS, NO, and IL-$1{\beta}$ production effectively. However, TMS inhibited $PGE_2$ levels only in high concentration ($300{\mu}g/m{\ell}$) and TMS failed to suppress the production of IL-6 and TNF-${\alpha}$. Results from immunoblot analyses revealed that TMS decreased activation of COX-2, iNOS, phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Conclusions : TMS has anti-RNS and anti-inflammatory effects via NF-${\kappa}B$ pathway and more intensive studies will be required to evaluate therapeutic potential of TMS.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.2
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• pp.194-201
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• 2016

The anti-inflammatory activity of ethanol extract from Chondrus nipponicus Yendo (CNYEE) was investigated by measuring production of a lipopolysaccharide-induced inflammatory response mediator. CNYEE had no cytotoxic effects on proliferation of macrophages compared to the control. CNYEE significantly inhibited (over 50%) NO production at $50{\mu}g/mL$, with inhibitory effects on expression levels of cytokines such as interleukin (IL)-6, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and IL-$1{\beta}$. In particular, IL-6 inhibitory activity of CNYEE was higher than 70% at $100{\mu}g/mL$. CNYEE also reduced protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor (NF)-${\kappa}B$ in a dose-dependent manner. CNYEE also significantly reduced phosphorylation of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Therefore, these results suggest that CNYEE may have anti-inflammatory effects by modulating the NF-${\kappa}B$ and mitogen-activated protein kinases signaling pathways and may be used as an anti-inflammatory therapeutic material.

• BMB Reports
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• v.41 no.11
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• pp.784-789
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• 2008

Mac-2BP is a ligand of the galectin family that has been suggested to affect tumor proliferation and metastasis formation. We assessed Mac-2BP expression at the transcriptional and translational levels to evaluate nerve growth factor (NGF)-induced Mac-2BP expression. A time kinetic analysis using reverse transcription-polymerase chain reaction showed that NGF-induced Mac-2BP transcript levels were 4-5 times higher than in controls. Mac-2BP enzyme-linked immunosorbent assay and immuno-fluorescence staining showed a 2-3-fold increase in intracellular and secreted Mac-2BP as a result of NGF stimulation. This increase was regulated by Akt activation and NF-${\kappa}B$ binding. p65 and p50-NF-${\kappa}B$ are major transcriptional factors in the Mac-2BP promoter region, and were shown to be regulated in accordance with the Akt activation states. Collectively, these results suggest that NGF induces Mac-2BP expression via the PI3K/Akt/NF-${\kappa}B$ pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.345-352
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• 2017

Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophage-mediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) and down-regulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-$1{\beta}$ without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the $NF-{\kappa}B$ transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of the $NF-{\kappa}B$ pathway, in LPS-stimulated RAW264.7 cells. However, JS-III-49 did not directly inhibit the kinase activities of Src and Syk, which are upstream kinases of Akt, in LPS-stimulated RAW264.7 cells. Moreover, JS-III-49 suppressed the nuclear translocation of c-Fos, one of the components of AP-1, by specifically targeting p38, an upstream mitogen-activated protein kinase (MAPK) in the AP-1 pathway in LPS-stimulated RAW264.7 cells. These results suggest that JS-III-49 plays an anti-inflammatory role in LPS-stimulated macrophages by targeting Akt and p38 in the $NF-{\kappa}B$ and AP-1 pathways, respectively.

• The Journal of Korean Medicine
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• v.29 no.1
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• pp.179-191
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• 2008

Background and Objectives : Atopic dermatitis is a recurrent or chronic eczematous skin disease with severe pruritus,and has increased in Korea. Although the pathogenic mechanisms of atopic dermatitis are yet unknown, recently skin barrier dysfunction and hyperresponsive Th2 cells in the acute phase have been reported as important mechanisms. Cheonggi-san(CGS) is used in oriental clinics for treatingacute skin lesions of eczema or urticaria. There have been no studies on the therapeutic mechanism of CGS for curing atopic dermatitis. We aimed to find out the therapeutic effects of its internaluse on atopic dermatitis-like skin lesions, induced in NC/Nga mice by the mite antigen D. pteronyssinus and disrupting skin barrier. Materials and Methods : The NC/Nga mice were classified into three groups: control group, atopic dermatitis elicitated group(AD), and CGS treated group (CT). Atopic dermatitis-like skin lesions were induced on the back of female NC/Nga mice, 12 weeks of age, by tape stripping, 5% SDS applied to disrupt skin barrier and painting 3 times a week with D. pteronyssinus crude extract solution for 3 weeks. CT was treated with CGS orally after atopic dermatitis was elicitated. We observed changes of skin damage, mast cells, substance P, angiogenesis, skin barrier, Th2 cell differentiation, nuclear factor-${\kappa}B(NF-{\kappa}B)$ p65 activation and COX-2 in NC/Nga mice with atopic dermatitis-like skin lesions. Results : The skin damages as eczema were seenin AD, but mitigated in CT. The degranulated mast cells in dermal papillae increased in AD, but decreased in CT. The substance P positive reacted cells in CT remarkably decreased. The angiogenesis increased in AD, but decreased in CT. The decrease of lipid deposition and ceramide in AD was seen, but anincrease of lipid deposition and ceramide in CT was seen. The distribution of IL-4 positive reacted cells in dermal papillae increased in AD, but decreased in CT. The distribution of NF-${\kappa}B$ p65 positive reacted cells & COX-2 positive reacted cells in CT decreased. Conclusion : The results may suggest that the CGS per os decreases the dysfunction of the skin barrier, inhibits Th2 cell differentiation and inhibits NF-${\kappa}B$ p65 activation in NC/Nga mice with atopic dermatitis-like skin lesions.