• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.97-101
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• 2011

Cirsium japonicum var. ussuriense is known to have a variety of biological activities, including anti-inflammatory, analgesic activity and antipyretic activity. In this study we investigated the role of polyacetylene compound, 1-Heptadecene-11, 13-diyne-8, 9, 10-triol (PA) from the root of Cirsium japonicum var. ussuriense as an immune-modulator. PA was evaluated as inhibitors of some macrophage functions involved in the inflammatory process. We tested the effect of PA on the production of pro-inflammatory cytokines, interleukin-1beta (IL-$1{\beta}$) and tumor necrosis factor-alpha (TNF-$\alpha$), and nitric oxide (NO) in murine macrophage cell line, RAW264.7. There was no effect on cytokine production of macrophages by PA itself. However, PA inhibited lipopolysaccharide (LPS)-induced IL-$1{\beta}$ and TNF-$\alpha$ production by macrophages at a dose dependent manner. PA also suppressed the NO production of macrophages by LPS. LPS-induced NF-${\kappa}B$ activity was decreased by treatment of PA. Therefore, these results suggest that PA has anti-inflammatory effect by inhibiting the NF-${\kappa}B$ activation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.10
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• pp.1527-1534
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• 2014

In this study, we investigated the anti-inflammatory effects of Lactobacillus rhamnosus fermented black garlic (FBG) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. FBG did not show cytotoxicity in RAW 264.7 cells at concentrations less than $800{\mu}g/mL$, and cell viability increased with FBG concentration. Nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production as well as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and IL-6 formation decreased in an FBG concentration-dependent manner, in LPS-induced RAW 264.7 cells. Furthermore, activation of LPS-inducible nitric synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-${\kappa}B$), and inhibitory kappa B ($I{\kappa}B$) protein expression was effectively inhibited by FBG treatment in LPS-induced RAW 264.7 cells. In contrast, heme oxygenase-1 (HO-1) protein expression significantly increased. These results indicate that the anti-inflammatory activity of FBG was due to activation of NF-${\kappa}B$, inhibition of cytokine production, and expression of iNOS and COX-2. From these results, we expect that FBG could contribute to the prevention and improvement of inflammatory disease.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.641-647
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• 2017

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-${\kappa}B$ activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, known to play an anti-inflammatory role. To investigate whether PPAR-${\gamma}$ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-${\gamma}$ antagonist before treatment of galangin. We found that PPAR-${\gamma}$ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-${\alpha}$ and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-${\kappa}B$, and PPAR-${\gamma}$ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

• Journal of Applied Biological Chemistry
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• v.61 no.2
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• pp.181-186
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• 2018

In this study, we investigated the anti-inflammatory activity of berberine using human monocytes. Infection of Propionibacterium acnes induced the production of nitric oxide (NO) and the pro-inflammatory cytokines such as, $TNF-{\alpha}$, IL-8 and $IL-1{\beta}$ in THP-1 monocytic cells. However, when berberine was supplemented in these P. acnes-induced THP-1 cells, the production of pro-inflammatory cytokines and NO was significantly reduced. We also analyzed signaling pathways of the antiinflammatory function of berberine and found that berberine suppressed the phosphorylation of ERK1/2, JNK and p38 and the expression and nuclear translocation of $NF-{\kappa}B$ p65 in the P. acnes-induced cells. From these results, we concluded that berberine can effectively exert the anti-inflammatory activity via suppressing the $NF-{\kappa}B$ and mitogen-activated protein kinases signaling pathways in human monocytes. Moreover, these results suggest the feasibility of developing natural therapeutics using berberine for the treatment of P. acnes-induced inflammatory diseases.

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.211-217
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• 2018

Hibiscus syriacus (H. syriacus) as the national flower of Korea has been used as the herbal medicine in Asia. In this study, we evaluated the anti-inflammatory effect of 70% ethanol extracts from the root of Hibiscus syriacus (RHS-E70) and elucidated the potential signaling pathway in LPS-stimulated RAW264.7 cells. RHS-E70 dose-dependently suppressed NO production by inhibiting iNOS and IL-${\beta}$ expression in LPS-stimulated RAW264.7 cells. RHS-E70 inhibited the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which contributed to the inhibition of p65 nuclear accumulation and NF-${\kappa}B$ activation. Furthermore, RHS-E70 suppressed the phosphorylation of ERK1/2 and p38, which results in the inhibition of ATF2 phosphorylation and subsequent nuclear accumulation. These results indicate that RHS-E70 may exert anti-inflammatory activity by inhibiting NF-${\kappa}B$ and MAPK/ATF2 signaling. From these findings, RHS-E70 has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.95.1-95
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• 2003

Ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol, a major pungent ingredient of ginger, inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying chemopreventive effects of [6]-gingerol on mouse skin carcinogenesis. Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins, has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. The murine COX-2 promoter contains several transcriptional elements, particularly those involved in regulating inflammatory processes. One of the essential transcription factors responsible for COX-2 induction is NF-kappa B. Topical application of [6]-gingerol inhibited the COX-2 expression through suppression of NF-kappa B activation in phorbol ester-treated mouse skin. [6]-Gingerol, through down-regulation of p38 MAPK, abrogated the DNA binding activity of NF-kappa B by blocking phosphorylation of p65/RelA at the Ser 536 residue. These findings suggest that [6]-gingerol exerts an anti-tumor promotional activity through inhibition of the p38 MAPK-NF-kappa B siganling cascade in mouse skin.

• Biomolecules & Therapeutics
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• v.21 no.5
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• pp.332-337
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• 2013

Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimer's disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-${\alpha}$ expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-${\kappa}B$ and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-${\kappa}B$/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.334-340
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• 2014

In this study, 23 oleanane-type triterpenoid saponins were isolated from a methanol extract of the roots of Pulsatilla koreana. The NF-${\kappa}B$ inhibitory activity of the isolated compounds was measured in $TNF{\alpha}$-treated HepG2 cells using a luciferase reporter system. Compounds 19-23 inhibited $TNF{\alpha}$-stimulated NF-${\kappa}B$ activation in a dose-dependent manner, with $IC_{50}$ values ranging from $0.75-8.30{\mu}M$. Compounds 19 and 20 also inhibited the $TNF{\alpha}$-induced expression of iNOS and ICAM-1 mRNA. Moreover, effect of the isolated compounds on PPARs transcriptional activity was assessed. Compounds 7-11 and 19-23 activated PPARs the transcriptional activity significantly in a dose-dependent manner, with $EC_{50}$ values ranging from $0.9-10.8{\mu}M$. These results suggest the presence of potent anti-inflammatory components in P. koreana, and will facilitate the development of novel anti-inflammatory agents.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.307-319
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• 2021

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.9
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• pp.1226-1234
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• 2012

3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.