• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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• pp.45-63
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• 2011

Objective : Atractyloides Chinensis Rhizome (ACR) is widely used in oriental medicine as a remedy for an inflammation and an allergic disease. However, as yet there is no clear explanation of how ACR affects the production of inflammatory cytokine. This study was to determine the effects of ACR on the mast cell-mediated inflammatory responses. Method : The amount of inflammatory cytokine production induced by the phorbol myristate acetate (PMA) plus calcium ionophore(A23187) in the human mast cell line (HMC-1) incubated with various concentrations of ACR was measured. The TNF-${\alpha}$ protein levels were analysised by Western blots. The TNF-${\alpha}$, IL-6 and IL-8 secreted protein levels were measured by the ELISA assay. The TNF-${\alpha}$, IL-6 and IL-8 mRNA levels were measured by the RT-PCR analysis. NF-${\kappa}$B, phospho-I${\kappa}$B and MAPKs were examined by Western blot analysis. The NF-${\kappa}$B promoter activity was examined by a luciferase assay. Results : 1. The expressions of TNF-${\alpha}$ and TNF-${\alpha}$ mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$. 2. The expressions of IL-6 and IL-6 mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$. 3. The expressions of IL-8 and IL-8 mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$ specially. 4. The expressions of Phosphorylated-JNK were decreased, not p38, ERK 5. The expressions of NF-${\kappa}$B were decreased dose-dependently at 0.1-0.2mg/$m\ell$ of ACR. The expressions of Phosphorylated I${\kappa}$B were significantly decreased at 0.2mg/$m\ell$. In addition, ACR suppressed PMA plus A23187-induced NF-${\kappa}$B promoting activity. Conclusion : It is suggested that ACR should suppress through inhibition of NF-${\kappa}$B activity and cytokine production.

• Herbal Formula Science
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• v.20 no.2
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• pp.83-92
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• 2012

Objectives : The aim of this study was to evaluate the efficacy of Hwangryunhaedok-tang (HHT) and Gungangbuja-tang (GBT) on lipopolysaccharide (LPS)-induced mouse model of inflammation. HHT and GBT are one of the representative prescriptions of cold drug and one of the representative prescriptions of hot drug, respectively. For experimental evaluation of their efficacy, we investigated the anti-inflammatory effects of HHT and GBT on LPS-induced inflammation and the mechanisms of their action. Methods : ICR mice were given a HHT (50, 500 mg/kg), GBT (100, 1000 mg/kg) extract orally on three consecutive days. On the third day, they were administered LPS intraperitoneally (35 mg/kg), 1 h after the last sample administration. Blood and liver samples were taken 6 h after the LPS challenge. Cytokine expression and inflammation-related protein factor analyses were performed by Western blotting. Results : Oral administration of HHT significantly reduced pro-inflammatory cytokines, including interleukin (IL)-6, and interferon (IFN)-${\gamma}$ in the serum. While GBT inhibited an increase of IL-6, IFN-${\gamma}$ was not affected. Immunoblot analysis showed that LPS-induced NF-${\kappa}b$ activation was inhibited by GBT, meanwhile HHT only inhibited NF-${\kappa}b$ expression at high does (500 mg/kg). In addition, HHT and GBT inhibited LPS-induced phosphorylation of Erk1/2, Jnk and p38 MAPKs. GBT also significantly inhibited i-Nos and Cox-2 expression, and HHT inhibited only i-Nos expression. Conclusions : Both of HHT and GBT showed anti-inflammatory effects against LPS-induced endotoxemia. However, HHT significantly decreased inflammatory cytokine levels, such as IL-6 and IFN-${\gamma}$ more than GBT, while GBT significantly inhibited inflammatory proteins, including NF-${\kappa}b$, MAP Kinases, i-Nos and Cox-2, more than HHT. These results suggest that HHT and GBT regulate the different mechanisms of action and pathways, presumably by regulating cytokine levels (IL-6, IFN-${\gamma}$), NF-${\kappa}b$ activation, and several pro-inflammatory gene expression, although both of HHT and GBT have anti-inflammatory effects.

• BMB Reports
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• v.47 no.2
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• pp.115-120
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• 2014

In this study, we show that Mycobacterium avium subsp. paratuberculosis MAP1305 induces the maturation of bone marrow-derived dendritic cells (BMDCs), a representative antigen presenting cell (APC). MAP1305 protein induces DC maturation and the production of pro-inflammatory cytokines (Interleukin (IL)-6), tumor necrosis factor (TNF)-${\alpha}$, and IL-$1{\beta}$) through Toll like receptor-4 (TLR-4) signaling by directly binding with TLR4. MAP1305 activates the phosphorylation of MAPKs, such as ERK, p38MAPK, and JNK, which is essential for DC maturation. Furthermore, MAP1305-treated DCs transform naive T cells to polarized $CD4^+$ and $CD8^+$ T cells, thus indicating a key role for this protein in the Th1 polarization of the resulting immune response. Taken together, M. avium subsp. paratuberculosis MAP1305 is important for the regulation of innate immune response through DC-mediated proliferation of $CD4^+$ and $CD8^+$ T cells.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• Journal of Life Science
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• v.29 no.11
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• pp.1251-1257
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• 2019

Peptidoglycan (PG) is found in atheromatous lesions of arteries, where monocytes/macrophages express inflammatory cytokines, including tumor necrosis factor-alpha ($TNF-{\alpha}$). This study investigated the effects of PG on $TNF-{\alpha}$ expression and examined possible cellular factors involved in $TNF-{\alpha}$ upregulation. The overall aim was to identify the molecular mechanisms underlying inflammatory responses to bacterial pathogen-associated molecular patterns in the artery. Exposure of human THP-1 monocytic cells to PG enhanced the secretion of $TNF-{\alpha}$ and induced its gene transcription. Inhibition of TLR-2/4 with OxPAPC significantly inhibited $TNF-{\alpha}$ gene expression, whereas inhibition of LPS by polymyxin B did not. The PG-induced expression of $TNF-{\alpha}$ was also significantly suppressed by pharmacological inhibitors that modulate activities of cellular signaling molecules; for example, U0126 (an ERK inhibitor), SB202190 (a p38 MAPK inhibitor), and SP6001250 (a JNK inhibitor) significantly attenuated PG-induced transcription of $TNF-{\alpha}$ and secretion of its gene product. $TNF-{\alpha}$ expression was also inhibited by rapamycin (an mTOR inhibitor), LY294002 (a PI3K inhibitor), and Akt inhibitor IV (an Akt inhibitor). ROS-regulating compounds, like NAC and DPI, also significantly attenuated $TNF{\alpha}$ expression induced by PG. These results suggest that PG induces $TNF-{\alpha}$ expression in monocytes/macrophages by multiple molecules, including TLR-2, PI3K, Akt, mTOR, MAPKs, and ROS.

• Journal of Life Science
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• v.31 no.2
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• pp.158-163
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• 2021

In the present study, we prepared hot water extracts of green apple (GAHW) and unripe apple (UAHW), and ethanol extract of green apple (GAE), and investigated their anti-inflammatory activities in LPS-activated RAW264.7 cells. All extracts dramatically suppressed nitric oxide (NO) production in a dose-dependent manner in LPS-stimulated RAW264.7 cells without affecting cell viability. In addition, all extracts decreased the expression of iNOS, whereas UAHW only reduced the expression of COX-2. All extracts suppressed the phosphorylation of MAPKs (p38, ERK, and JNK) indicating all extracts show their anti-inflammatory activities via regulating MAPK pathway. Furthermore, all extracts reduced the production of reactive oxygen species in a dose-dependent manner and they increased the expression of heme oxygenase-I (HO-I) whereas UAHW could not. We also investigated whether apple flavonoids phloretin and phloridzin can have their anti-inflammatory activities in same in vitro model. Phloretin dramatically decreased NO production in a dose dependent manner without affecting cell viability, whereas phloridzin have no effects. Phloretin also reduced the expression of iNOS as well as COX-2, whereas phloridzin could not. Overall, these results suggest that apple extracts have their anti-inflammatory activities via regulating MAPKs and HO-1 pathways, and apple flavonoid phloretin can be one of phytochemicals responsible for anti-inflammatory effect of apple.

• Journal of Life Science
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• v.20 no.11
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• pp.1603-1610
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• 2010

Fucoidans are sulfated fucosylated polymers from the cell wall of brown algae. We assessed the effects of Fucus evanescens fucoidan on ultraviolet-B (UVB)-induced expression of matrix metalloproteinase-1 (MMP-1) protein, mRNA, and promoter, and the phosphorylation of mitogen-activated protein kinases in vitro using an immortalized human keratinocyte cell line. Pretreatment with 10 and $100\;{\mu}g/ml$ fucoidan significantly inhibited UVB-induced MMP-1 protein, mRNA and promoter activity, compared to UVB irradiation alone. Extracellular signal regulated kinase activation was markedly inhibited by treatment with fucoidan, though c-JUN N-terminal kinase activity and p38 activation were only marginally affected by fucoidan. F. evanescens fucoidan may be a potential therapeutic agent for the prevention and treatment of skin photoaging.

• Korean Journal of Food Science and Technology
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• v.50 no.5
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• pp.555-563
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• 2018

Barley has nutritional benefits due to its high dietary fiber content; therefore, the intake of whole barley grains is recommended. However, barley is often consumed in the fermented form because of the improved texture and digestibility. The present study was designed to elucidate the intracellular signaling pathway for macrophage activation by the polysaccharide BF-CP from fermented barley. BF-CP is a neutral polysaccharide, composed of neutral sugars, including glucose (70.7%), xylose (11.4%), and arabinose (9.0%). BF-CP exhibited macrophage-stimulatory activity by inducing the production of interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, and nitric oxide in RAW 264.7 macrophages. Further, BF-CP treatment strongly increased the IL-6 and $TNF-{\alpha}$ gene expression in a concentration-dependent manner. Signal transduction experiments using immunoblotting showed that BF-CP phosphorylated mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38, and nuclear factor $(NF)-{\kappa}B$, in RAW 264.7 cells in a concentration-dependent manner. These results suggest that BF-CP activates the macrophages via MAPK and $NF-{\kappa}B$ pathways, and also induces an increase in the production of cytokines.

• Journal of Life Science
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• v.31 no.10
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• pp.898-904
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• 2021

Locusta migratoria is a widespread locust species in many parts of the world and is considered an alternative source for the production of protein for value-added ingredients. We previously identified putative antimicrobial peptides derived from L. migratoria through an in silico analysis of its transcriptome. However, its anti-inflammatory effect has not been studied. In this study, we investigated the anti-inflammatory activities of the antimicrobial peptide locustacin (KTHILSFFPSFLPLFLKK-NH₂) derived from L. migratoria on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Locustacin (50, 100, and 200 ㎍/ml) significantly reduced the production of nitric oxide (NO) in LPS-stimulated macrophages without any cytotoxicity. Locustacin also inhibited the mRNA and protein expression of pro-inflammatory mediators, such as inducible NO synthase and cyclooxygenase-2, in contrast to the presence of LPS alone. Locustacin decreased the release of LPS-induced pro-inflammatory cytokines, including interleukin (IL)-6 and IL-1β, and their gene expression in a dose-dependent manner. Furthermore, locustacin (100 and/or 200 ㎍/ml) inhibited phosphorylation levels of extracellular signal regulated kinase, p38, and c-Jun N-terminal kinase. Locustacin also suppressed the degradation of inhibitory kappa B alpha, which was considered to be an inhibitor of nuclear factor kappa B (NF-κB). Collectively, these results demonstrate that locustacin can exert anti-inflammatory effects through the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation, activation of NF-κB, and downstream inflammatory mediators in LPS-stimulated macrophage cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.11
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• pp.1612-1620
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• 2015

Inflammation is a complex process involving a variety of immune cells, which defend the body from harmful stimuli. However, pro-inflammatory cytokines and inflammatory mediators can also exacerbate diseases such as cancer. Onion peel contains several phenolic compounds, including quercetin at an amount 20 times greater in peel than edible flesh. Therefore, in this study, the anti-inflammatory effects of onion peel ethanol extract (OPEE) were investigated lipopolysaccharide-induced inflammatory response. In our results, NO production decreased in a dose-dependent manner. Secretion of IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$ was suppressed by 44%, 53%, and 60% respectively, at $100{\mu}g/mL$. Moreover, OPEE also suppressed expression of COX-2, iNOS, $NF-{\kappa}B$, and MAPKs in a dose-dependent manner. Formation of mice ear edema was reduced at the highest dose tested compared to the control, and reduction of ear thickness was observed in the histological analysis as well. In the acute toxicity test, no morality was observed in mice administered 5,000 mg/kg body weight of OPEE over a 2-week observation period. These results suggest that OPEE may have significant effects on inflammatory factors and be a potential anti-inflammatory material.