• Journal of Periodontal and Implant Science
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• v.41 no.3
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• pp.157-163
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• 2011

Purpose: Curcumin is known to exert numerous biological effects including anti-inflammatory activity. In this study, we investigated the effects of curcumin on the production of interleukin-6 (IL-6) by murine macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory periodontal disease, and sought to determine the underlying mechanisms of action. Methods: LPS was prepared from lyophilized P. intermedia ATCC 25611 cells by the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time polymerase chain reaction to detect IL-6 mRNA expression. $I{\kappa}B-{\alpha}$ degradation, nuclear translocation of NF-${\kappa}B$ subunits, and STAT1 phosphorylation were characterized via immunoblotting. DNA-binding of NF-${\kappa}B$ was also analyzed. Results: Curcumin strongly suppressed the production of IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW 264.7 cells. Curcumin did not inhibit the degradation of $I{\kappa}B-{\alpha}$ induced by P. intermedia LPS. Curcumin blocked NF-${\kappa}B$ signaling through the inhibition of nuclear translocation of NF-${\kappa}B$ p50 subunit. Curcumin also attenuated DNA binding activity of p50 and p65 subunits and suppressed STAT1 phosphorylation. Conclusions: Although further study is required to explore the detailed mechanism of action, curcumin may contribute to blockade of the host-destructive processes mediated by IL-6 and appears to have potential therapeutic values in the treatment of inflammatory periodontal disease.

• Korean Journal of Veterinary Research
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• v.51 no.3
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• pp.217-225
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• 2011

Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B ($NF{\kappa}B$) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, $NF{\kappa}B$ activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of $NF{\kappa}B$ activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of $NF{\kappa}B$ and phospho-$I{\kappa}B$ proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of $NF{\kappa}B$ and phospho-$I{\kappa}B$ significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of $NF{\kappa}B$ and phophorylation of $I{\kappa}B$ in the CNS. Subsequently, the inhibition of $NF{\kappa}B$ activation and $I{\kappa}B$ phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.2
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• pp.166-183
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• 2008

Purpose: This study was performed to determine anti-imflammatory effects of Haedoksamultang. Methods: In this study, I examined the effects of Haedoksamultang on the production of nitric oxide(NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), and interlukin-1${\beta}$(IL-1${\beta}$) as well as the expression of inducible NO synthase(iNOS), cyclooxygenase-2(COX-2), TNF-${\alpha}$, and IL-1${\beta}$ in RAW 264.7 cells. Haedoksamultang inhibited LPS-stimulated NO production. Western blotting and RT-PCR analysis showed that Haedoksamultang suppressed LPS-induced iNOS and COX-2 protein and mRNA expression in RAW 264.7 cells. Haedoksamultang also suppressed the expression and production of LPS-stimulated TNF-${\alpha}$ and IL-1${\beta}$ in RAW 264.7 cells. Haedoksamultang inhibited NF-${\kappa}B$ activation in LPS-treated RAW 264.7 cells. Moreover, this compound blocked $I{\kappa}B-{\alpha}$ phosphorylation and nuclear translocation of the cytosolic NF-${\kappa}B$ p65 subunit, which highly correlated with the production and expression of inflammatory mediators. Results: Haedoksamultang suppresses that inflammation-associated gene expression by blocking NF-${\kappa}B$ activation. Conclusion: These results suggest that Haedoksamultang may be beneficial for treating inflammatory disease.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.10-16
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• 2014

Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$ and TNF-${\alpha}$. In addition, methyl p-hydroxycinnamate 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. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.489-495
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• 2022

Background: Although ginsenosides and saponins in Korea red ginseng (KRG) shows various pharmacological roles, their roles in the inflammatory response are little known. This study investigated the anti-inflammatory role of ginsenosides identified from KRG saponin fraction (RGSF) and the potential mechanism in macrophages. Methods: The ginsenoside composition of RGSF was identified by high-performance liquid chromatography (HPLC) analysis. An anti-inflammatory effect of RGSF and its mechanisms were studied using nitric oxide (NO) and prostaglandin E₂ (PGE₂) production assays, mRNA expression analyses of inflammatory genes and cytokines, luciferase reporter gene assays of transcription factors, and Western blot analyses of inflammatory signaling pathways using the lipopolysaccharide (LPS)-treated RAW264.7 cells. Results: HPLC analysis identified the types and amounts of various panaxadiol ginsenosides in RGSF. RGSF reduced the generation of inflammatory molecules and mRNA levels of inflammatory enzymes and cytokines in LPS-treated RAW264.7 cells. Additionally, RGSF inhibited the signaling pathways of NF-κB and AP-1 by suppressing both transcriptional factors and signaling molecules in LPS-treated RAW264.7 cells. Conclusion: RGSF contains ginsenosides that have anti-inflammatory action via restraining the NF-κB and AP-1 signaling pathways in macrophages during inflammatory responses.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.463-469
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• 2010

This research is performed to obtain positive evidences of Mori cortex, a kind of oriental medicinal herbs, in the cellular levels. The extracts of M. cortex have shown anti-inflammatory effects against cutaneous inflammation and clinical effects on pulmonary asthma and congestion in oriental medicine. Thus BV2 cells were chosen because microglia are considered as the main immunocompetent cells in the central nervous system. Lipopolysaccharide (LPS)-induced microglial activation of cultured BV2 cells and subsequent release of nitric oxide (NO) and Prostaglandin E2 (PGE2) were effectively suppressed by methylene chloride extract of Morus alba L. (MEMA). From the inflammation-mediated mRNA and protein analyses, we showed that inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumor necrosis alpha (TNF-${\alpha}$) induced by LPS were markedly decreased by MEMA treatment. From the observation of nuclear factor-kB (NF-${\kappa}B$) which is controlling and mediating inflammation through COX-2 and iNOS, there showed that p65, a subunit of NF-${\kappa}B$, was increased in nuclear and $I{\kappa}B$, a competitor of NF-${\kappa}B$, was recovered in cytosol after MEMA treatment. These are corresponding with results of iNOS, COX-2, IL-$1{\kappa}$ and TNF-${\alpha}$, and confirm some suppressive effect against transcriptional activation of NF-${\kappa}B$. In conclusion, the anti-inflammatory action of M. cortex against BV2 microglia cells is expected to protect nerve tissues through suppression of neuronal inflammation in various neurodegenerative diseases.

• Nutrition Research and Practice
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• v.11 no.4
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• pp.265-274
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• 2017

BACKGROUND/OBJECTIVES: Nelumbo leaves have been used in traditional medicine to treat bleeding, gastritis, hemorrhoids, and halitosis. However, their mechanisms have not been elucidated. MATERIALS/METHODS: The present study prepared two Nelumbo leaf extracts (NLEs) using water or 50% ethanol. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 and nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) productions were assessed. To determine the anti-inflammatory mechanism of NLEs, we measured nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity. Major metabolites of NLEs were also analyzed and quantified. RESULTS: NLEs effectively reduced the expression and productions of pro-inflammatory mediators such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, $PGE_2$, and NO. NLEs also reduced NF-${\kappa}B$ activity by inhibiting inhibitor of NF-${\kappa}B$ phosphorylation. Both extracts contained catechin and quercetin, bioactive compounds of NLEs. CONCLUSIONS: In this study, we showed that NLEs could be used to inhibit NF-${\kappa}B$-mediated inflammatory responses. In addition, our data support the idea that NLEs can ameliorate disease conditions involving chronic inflammation.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.331-335
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• 2011

In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-$1{\beta}$, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-${\kappa}B$ and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.

• Journal of Microbiology and Biotechnology
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• v.18 no.12
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• pp.1984-1989
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• 2008

Surfactin is a natural biosurfactant derived from Bacillus subtilis and has various biological activities such as anticancer, antiplatelet, and anti-inflammatory effects. In this study, the inhibitory mechanism of surfactin in NO production from macrophages was examined. Surfactin down regulated LPS-induced NO production in RAW264.7 cells and primary macrophages with $IC_{50}$ values of 31.6 and $22.4{\mu}M$, respectively. Immunoblotting analysis showed that surfactin strongly blocked the phosphorylation of IKK and $l{\kappa}B{\alpha}$ and the nuclear translocation of $NF-{\kappa}B$ (p65). Therefore, these data suggest that surfactin may act as a bacterium-derived anti-inflammatory agent with anti-$NF-{\kappa}B$ activity.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.1-12
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• 2008

Background and Objectives: Sinusitis is a common disease in the otorhinolaryngology field. It is inflammatory change of the mucous membrane which surrounds the sinus. The aim of this study was to investigate the anti-inflammatory effects of the Taklisodok-eum (TSE) extract on the mouse model with acute sinusitis induced by S. pneumoniae. Methods: Thirty six-week-old male BALB/c mice were divided into three groups: the normal group, the group inoculated with S. pneumoniae which caused allergic rhinitis (control group), and the group treated with the TSE extract after it was treated the same as the control group (sample group). Results: $NF-{\kappa}B$ activation was suppressed, and iNOS & COX-2 production were inhibited by TSE in acute sinusitis. Apoptosis was increased by TSE in acute sinusitis. The number of eosinophils in the sample group noticeably decreased when compared to the control group. In the general morphologic change, the increase of damaged respiratory ciliated epithelia & eosinophils' infiltration was lessin the sample group. Goblet cells were maintained in the sample group. MMP-9, HSP-70 and BrdU decreased in the sample group. Apocrine secretion decreased in the sample group. Conclusion: The findings in this study show that TSE reduces acute sinusitis through its anti-inflammatory effects, such as the inhibition of $NF-{\kappa}B$ activity.