• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.532-537
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• 2012

Avicularin, quercetin-3-${\alpha}$-L-arabinofuranoside, has been reported to possess diverse pharmacological properties such as anti-inflammatory and anti-infectious effects. However, the underlying mechanism by which avicularin exerts its anti-inflammatory activity has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of avicularin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Avicularin significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein levels of iNOS and COX-2, which are responsible for the production of NO and $PGE_2$, respectively. Avicularin also suppressed LPS-induced overproduction of pro-inflammatory cytokine IL-$1{\beta}$. Furthermore, avicularin significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-${\kappa}B$ in the nucleus. To understand the underlying signaling mechanism of anti-inflammatory activity of avicularin, involvement of multiple kinases was examined. Avicularin significantly attenuated LPS-induced activation of ERK signaling pathway in a concentration-dependent manner. Taken together, the present study clearly demonstrates that avicularin exhibits anti-inflammatory activity through the suppression of ERK signaling pathway in LPS-stimulated RAW 264.7 macrophage cells.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.2
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• pp.1-15
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• 2017

Objectives: The object of this study was to identify the anti-inflammatory effects of Patrinia scabiosaefolia aqueous extract (PSE). Methods: RAW 264.7 cells were pre-treated with PSE and then incubated with or without lipopolysaccharide (LPS). Cell viability, production of nitric oxide (NO), secretion of pro-inflammatory cytokine, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-${\kappa}B$) were measured. In addition, we observed mice survival rate after LPS and their cytokine levels of serum. We also observed inflammatory and hemorrhagic change on the histological sections of the liver. Results: PSE inhibited LPS-induced NO production, interleukin (IL)-6 secretion, c-Jun NH2-terminal kinase (JNK) and NF-${\kappa}B$ activation. In addition, PSE reduced the death rate of LPS-induced mice and IL-6 production on the serum of mice. PSE inhibited inflammation and hemorrhage on liver tissue as well. Conclusions: The results suggest that PSE have anti-inflammatory effects by inhibited NF-${\kappa}B$ and JNK activation, IL-6 secretion, and NO production. So PSE may be effective treatment for the inflammatory disease.

• BMB Reports
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• v.41 no.4
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• pp.328-333
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• 2008

A variety of anti-inflammatory agents have been shown to exert chemopreventive activity via targeting of transcription factors such as NF-${\kappa}B$ and AP-1. Lithospermum erythrorhizon (LE) has long been used in traditional oriental medicine. In this study, we demonstrated the inhibitory effects of LE extracts on lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines. As an underlying mechanism of inhibition, LE extracts reduced LPS-induced transactivation of AP-1 as well as NF-${\kappa}B$ in mouse macrophage cells. Electrophoretic mobility shift assays indicated that LE extracts inhibited the DNA binding activities of AP-1 and NF-${\kappa}B$. In addition, phosphorylation of $I{\kappa}B-{\alpha}$ protein was suppressed by LE extracts. Moreover, LE extracts inhibited c-Jun N-terminal kinase and extracellular signal-regulated signaling pathways. Our results suggest that the anti-inflammatory activity of LE extracts may be mediated by the inhibition of signal transduction pathways that normally lead to the activation of AP-1and NF-${\kappa}B$. These inhibitory effects may be useful for chemoprevention of cancer or other chronic inflammatory diseases.

• Korean Journal of Food Science and Technology
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• v.44 no.6
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• pp.759-762
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• 2012

Egg allergies have been reported as one of the most prevalent food hypersensitivities in the pediatric population. One of the major egg allergens is ovalbumin (OVA), which is the major protein in the egg whites. Phenethyl isothiocyanate (PEIC) from cruciferous vegetables has an effect on anti-inflammatory therapy. In the present report, we show that PEIC inhibits the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activation induced by OVA. PEIC also inhibits the OVA-induced inducible nitric oxide synthase (iNOS) expression and nitrite production. However, PEIC did not suppress the cyclooxygenase-2 (COX-2) expression induced by OVA. These results suggest that PEIC has the specific mechanism for anti-inflammatory responses and efficient anti-allergic activities.

• Journal of the Korean Society of Food Culture
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• v.33 no.4
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• pp.337-344
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• 2018

Germinated brown rice (GBR, Orysa sartiva L.) has been reported to have anti-obesity and anti-inflammatory effects. However, the mechanisms underlying these effects in adipocytes are not fully understood. Therefore, this study was conducted to explore the anti-inflammatory mechanisms of GBR on lipopolysaccharide (LPS)-stimulated 3T3-L1 adipocytes. 3T3-L1 adipocytes were pretreated with GBR extracts (0-20 mg/mL) 1 h before LPS stimulation. The mRNA expression of adipokines and Toll-like receptor 4 (TLR4) were measured by RT-PCR. The protein expressions of TLR4-related molecules were detected by western blotting and nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) activation was measured. Our results showed that GBR extract dose-dependently inhibited mRNA expression of LPS-induced tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). GBR extract was found to inhibit LPS-induced mRNA expression of TLR4 and protein expression of both myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factor 6 (TRAF6). Furthermore, GBR extract significantly inhibited extracellular receptor-activated kinase (ERK) phosphorylation and $NF-{\kappa}B$ activation. These results suggest that GBR extract has the anti-inflammatory effects on LPS-induced inflammation via inhibition of TLR4 signaling, includingthe ERK and $NF-{\kappa}B$ signaling pathways, in adipocytes.

• Biomedical Science Letters
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• v.18 no.4
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• pp.345-354
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• 2012

Angelica keiskei has exhibited numerous pharmacological effects including antitumor, antimetastatic, and antidiabetic effects. However, the anti-inflammatory effects and mechanisms employed by xanthoangelol E isolated from Angelica keiskei are incompletely understood. In this study, we attempted to determine the effects of Xanthoangelol E on the lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophage. The findings of this study demonstrated that xanthoangelol E inhibited the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and prostaglandin $E_2$ ($PGE_2$). Xanthoangelol E inhibited the enhanced levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) caused by LPS. Additionally, we showed that the anti-inflammatory effect of xanthoangelol E is through the regulation of the activation of nuclear factor (NF)-${\kappa}B$ and caspase-1. These results provide novel insights into the pharmacological actions of xanthoangelol E as a potential candidate for the development of new drugs to treat inflammatory diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.6
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• pp.922-928
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• 2012

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is one of the most abundant isothiocyanates in some cruciferous vegetables, especially broccoli. Sulforaphaene has been shown to exhibit many pharmacological activities, including anti-oxidant, anti-inflammatory and anti-microbial activities. However, the anti-skin photoaging effects of sulforaphane have not yet been reported. In the present study, we investigated the inhibitory effects of sulforaphane on MMP-1 and -3 expressions of the human dermal fibroblasts via various in vitro experiments and elucidated the pathways of inhibition. Western blot analysis and real-time PCR revealed sulfiraphane inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, which was determined by NF-${\kappa}B$ DNA binding activity. UVB-induced NF-${\kappa}B$ activation and MMP expression were completely blocked by sulforphane. These findings suggest that sulforaphane could prevent UVB-induced MMPs expressions through inhibition of NF-${\kappa}B$ activation.

• Natural Product Sciences
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• v.24 no.1
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• pp.13-20
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• 2018

Estragole is a naturally occurring phenylpropanoid obtained from essential oils found in a broad diversity of plants. Although the phenylpropanoids show many biological activities, clear regulation of the inflammatory signaling pathways has not yet been determined. Here, we scrutinized the anti-inflammatory effect of estragole. The anti-inflammatory effect of estragole was determined through the inhibitory mechanisms of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), nuclear factor kappa B ($NF-{\kappa}B$), and mitogen-activated protein kinases (MAPK) pathways and the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2)/heme oxygenase (HO)-1 pathways in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Estragole significantly inhibited NO production, iNOS and COX-2 expression as well as LPS-induced $NF-{\kappa}B$ and MAPK activation. Furthermore, estragole suppressed LPS-induced intracellular ROS production but up-regulated the stress response gene HO-1 via the activation of transcription factor Nrf-2. These findings demonstrate that estragole inhibits the LPS-induced expression of inflammatory mediators via the down-regulation of iNOS, COX-2, $NF-{\kappa}B$, and MAPK pathways, as well as the up-regulation of the Nrf-2/HO-1 pathway, indicating that this phenylpropanoid has potential therapeutic and preventive applications in various inflammatory diseases.

• Tuberculosis and Respiratory Diseases
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• v.68 no.3
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• pp.168-174
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• 2010

Background: Sepsis still has a high mortality rate despite adequate supportive care. Newer therapeutic modalities have been developed but they have generally ended in failure. Recently, insulin was reported to have an anti-inflammatory effect by inhibiting the $I{\kappa}B/NF-{\kappa}B$ pathway, and may have therapeutic potential in sepsis. However, the precise mechanism of the anti-inflammatory effect of insulin is unclear. This study examined the role of insulin in activating $I{\kappa}B/NF-{\kappa}B$ in macrophage. Methods: Raw 264.7 cells, a murine macrophage cell line, were used in this experiment. Western blotting using $I{\kappa}B$ Ab and phosphor-specific $I{\kappa}B$ Ab was performed to evaluate the degradation and phosphorylation of $I{\kappa}B$ cells. For the $I{\kappa}B$ Kinase (IKK) activity, an immune complex kinase assay was performed. The level of interleukin-6 (IL-6) was measured by ELISA to determine the level of proinflammatory cytokine. Results: $I{\kappa}B{\alpha}$ degradation began 30 min after lipopolysaccharide (LPS) treatment. However, an insulin pretreatment suppressed the $I{\kappa}B{\alpha}$ degradation caused by the LPS treatment. The phosphorylation of $I{\kappa}B{\alpha}$ and IKK activity was also inhibited by the insulin pretreatment. Finally, the insulin pretreatment showed a tendency to suppress the induction of IL-6 by LPS. Conclusion: Insulin might have an anti-inflammatory effect though partial inhibition of the $I{\kappa}B/NF{\kappa}B$ pathway in macrophage cell lines.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.1
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• pp.75-81
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• 2017

Dangguisoo-san (DGSS), a traditional Korean herbal formula, has been prescribed to patients who suffer from various symptoms related with blood stagnation. Since inflammation can cause blood stagnation, we hypothesized that DGSS suppresses inflammation, relieving the symptoms associated with blood stagnation. In this study, given that DGSS is prepared in a mix of alcohol and water, we prepared the methanol (mDGSS) and water extract (wDGSS) of DGSS and compared their activities in suppressing inflammatory reaction. Western blot analyses show that mDGSS was more effective than wDGSS in activating Nrf2, a key factor that suppresses inflammation. Semi-quantitative RT-PCR shows that mDGSS activating Nrf2 resulted in the induction of Nrf2-dependent genes expression. However, mDGSS was not effective in suppressing the nuclear translocation of $NF-{\kappa}B$, a key factor that promotes inflammation, and the expression of $NF-{\kappa}B$-dependent genes such as TNF-a and IL-1b. When comparing with wDGSS, mDGSS was less effective in suppressing luciferase activity driven by $NF-{\kappa}B$. Therefore, our results show that mDGSS has the anti-inflammatory function by mainly activating Nrf2, while wDGSS does by both activating Nrf2 and suppressing $NF-{\kappa}B$. Our results suggest that preparing DGSS in a mix of water and methanol is a better way to achieve a strong anti-inflammatory efficacy of DGSS.