• Food Science and Biotechnology
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• v.17 no.6
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• pp.1294-1298
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• 2008

Toll-like receptors (TLRs) induce innate immune responses recognizing conserved microbial structural molecules. All TLR signaling pathways culminate in the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$). The activation of NF-${\kappa}B$ leads to the induction of inflammatory gene products such as cyclooxygenase-2 (COX-2). Guggul has been used for centuries to treat a variety of diseases. Guggulstreone, one of the active ingredients in guggul, has been used to treat many chronic diseases. However, the mechanism as to how guggulsterone mediate the health effects is largely unknown. Here, we report biochemical evidence that guggulsterone inhibits the NF-${\kappa}B$ activation and COX-2 expression induced by TLR2, TLR3, and TLR4 agonists. Guggulsterone also inhibits the NF-${\kappa}B$ activation induced by downstream signaling components of TLRs, myeloid differential factor 88 (MyD88), $I{\kappa}B$ kinase ${\beta}$ ($IKK{\beta}$), and p65. These results imply that guggulsterone can modulate the immune responses regulated by TLR signaling pathways.

• Korean Journal of Agricultural Science
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• v.46 no.3
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• pp.653-660
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• 2019

Ganoderma lucidum, an oriental polypore fungus and medicinal mushroom, has a long history of use for promoting health and longevity in Korea, China, and other Asian countries. This study was aimed at determining the anti-inflammatory activity and mechanism of action of Ganoderma lucidum in murine macrophage RAW 264.7 cells. Ganoderma lucidum was extracted with ethanol and freeze-dried. The anti-inflammatory effect (nitrite production) of Ganoderma lucidum extracts was tested using a nitric oxide (NO) colorimetric assay. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to quantify the mRNA expression of cytokines including tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6. Western blotting was performed to measure the expression levels of inflammation-related proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor kappa B ($NF-{\kappa}B$) p65, and phosphorylated $NF-{\kappa}B$ p65. The NO colorimetric assay showed that NO production increased with the treatment of lipopolysaccharide in (LPS)-activated RAW 264.7 macrophages and decreased with the cotreatment of Ganoderma lucidum extracts and LPS. Ganoderma lucidum extracts repressed the mRNA expressions of cytokines, which were increased after the LPS treatment. In addition, Ganoderma lucidum extracts inhibited the LPS-induced expression of iNOS and COX-2 and the LPS-induced phosphorylation of $NF-{\kappa}B$ p65. These results suggest that the Ganoderma lucidum extracts exert an anti-inflammatory activity by inhibiting $NF-{\kappa}B$ related proteins and cytokines.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.303-310
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• 2021

In the present study, kaempferol, a flavonoidal natural compound found in Polygonati Rhizoma, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. A human respiratory epithelial NCI-H292 cells was pretreated with kaempferol for 30 min and stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway or EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was investigated. Kaempferol suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IκBα), and NF-κB p65 nuclear translocation. Also, kaempferol inhibited EGF-induced gene expression and production of MUC5AC mucin through regulating the phosphorylation of EGFR, phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These results suggest kaempferol regulates the gene expression and production of mucin through regulation of NF-κB and MAPK signaling pathways, in human airway epithelial cells.

• Journal of Microbiology and Biotechnology
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• v.30 no.4
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• pp.490-496
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• 2020

Consumption of anti-inflammatory nutraceuticals may help treat or prevent inflammation-related illnesses such as diabetes, cardiovascular disease, and cancer. This study evaluated the effect of Croton hirtus L'Hér extract (CHE) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor kappa-B (NF-κB) signaling cascades. CHE significantly suppressed LPS-induced NO production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophages, although cyclooxygenase (COX)-2 expression was not affected. CHE also suppressed LPS-induced IκB kinase (IKK), IκB, and p65 phosphorylation in RAW264.7 cells. Western blot and immunofluorescence assays of cytosol and nuclear p65 and the catalytic subunit of NF-κB showed that CHE suppressed LPS-induced p65 translocation from the cytosol to the nucleus. CHE also suppressed LPS-induced Interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in RAW264.7 cells. These results suggest that CHE prevents NO-mediated inflammation by suppressing NF-κB and inflammatory cytokines.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9835-9839
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• 2014

Fisetin is an effective compound extracted from lacquer which has been used in the treatment of various diseases. Preliminary data indicate that it also exerts specific anti-cancer effects. However, the manner in which fisetin regulates cancer growth remains unknown. In this study, we elucidated interference of fisetin with targets of the nuclear factor ${\kappa}B$ signal transduction pathway activated by Epstein-Barr virus encoding latent membrane protein 1 (LMP1)in nasopharyngeal carcinoma (NPC) cells, Results showed that fisetin inhibited the survival rate of CNE-LMP1 cells and NF-${\kappa}B$ activation caused by LMP1. Fisetin also suppressed nuclear translocation of NF-${\kappa}B$ (p65) and $I{\kappa}B{\alpha}$ phosphorylation, while inhibiting CyclinD1, all key targets of the NF-${\kappa}B$ signal transduction pathway. It was suggested that interference effects of fisetin with signal transduction activated by LMP1 encoded by the Epstein-Barr virus may play an important role in its anticancer potential.

• Journal of Nutrition and Health
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• v.50 no.1
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• pp.25-31
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• 2017

Purpose: Neuroinflammation is mediated by activation of microglia implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Petalonia binghamiae is known as a traditional food, based on multiple biological activities such as anti-oxidant and anti-obesity. In present study, the anti-neuroinflammatory potential of Petalonia binghamiae was investigated in LPS-stimulated BV2 microglial cells. Methods: Cell viability was measured by MTT assay. Production of nitric oxide (NO) was examined using Griess reagent. Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by Western blot analysis. Activation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$) signaling was examined by nuclear translocation of $NF-{\kappa}B$ p65 subunit and phosphorylation of $I{\kappa}B$. Results: Extract of Petalonia binghamiae significantly inhibited LPS-stimulated NO production and iNOS/COX-2 protein expression in a dose-dependent manner without cytotoxicity. Pretreatment with Petalonia binghamiae suppressed LPS-induced $NF-{\kappa}B$ p65 nuclear translocation and phosphorylation of $I{\kappa}B$. Co-treatment with Petalonia binghamiae and pyrrolidine duthiocarbamate (PDTC), an $NF-{\kappa}B$ inhibitor, reduced LPS-stimulated NO release compared to that in PB-treated or PDTC-treated cells. Conclusion: The present results indicate that extract of Petalonia binghamiae exerts anti-neuroinflammation activities, partly through inhibition of $NF-{\kappa}B$ signaling. These findings suggest that Petalonia binghamiae might have therapeutic potential in relation to neuroinflammation and neurodegenerative diseases.

• The Korean journal of internal medicine
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• v.34 no.1
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• pp.146-155
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• 2019

Background/Aims: Indoxyl sulfate (IS) is a uremic toxin and an important causative factor in the progression of chronic kidney disease. Recently, paricalcitol (19-nor-1,25-dihydroxyvitamin D2) was shown to exhibit protective effects in kidney injury. Here, we investigated the effects of paricalcitol treatment on IS-induced renal tubular injury. Methods: The fluorescent dye 2',7'-dichlorofluorescein diacetate was used to measure intracellular reactive oxygen species (ROS) following IS administration in human renal proximal tubular epithelial (HK-2) cells. The effects of IS on cell viability were determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and levels of apoptosis-related proteins (Bcl-2-associated protein X [Bax] and B-cell lymphoma 2 [Bcl-2]), nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65, and phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) were determined by semiquantitative immunoblotting. The promoter activity of $NF-{\kappa}B$ was measured by luciferase assays and apoptosis was determined by f low cytometry of cells stained with f luorescein isothiocyanate-conjugated Annexin V protein. Results: IS treatment increased ROS production, decreased cell viability and induced apoptosis in HK-2 cells. IS treatment increased the expression of apoptosis-related protein Bax, decreased Bcl-2 expression, and activated phosphorylation of MAPK, $NF-{\kappa}B$ p65, and Akt. In contrast, paricalcitol treatment decreased Bax expression, increased Bcl-2 expression, and inhibited phosphorylation of MAPK, $NF-{\kappa}B$ p65, and Akt in HK-2 cells. $NF-{\kappa}B$ promoter activity was increased following IS, administration and was counteracted by pretreatment with paricalcitol. Additionally, flow cytometry analysis revealed that IS-induced apoptosis was attenuated by paricalcitol treatment, which resulted in decreased numbers of fluorescein isothiocyanate-conjugated Annexin V positive cells. Conclusions: Treatment with paricalcitol inhibited IS-induced apoptosis by regulating MAPK, $NF-{\kappa}B$, and Akt signaling pathway in HK-2 cells.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.385-393
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• 2008

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we evaluated the effects of the methanol extract of Polytrichum commune Hedw (PCM) (Polytrichaceae) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines release in murine macrophage cell line RAW 264.7. PCM potently inhibits the production of NO, $PGE_2$, tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-6. Consistent with these results, PCM also concentration-dependently inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygase (COX)-2 at the protein levels, and iNOS, COX-2, TNF-$\alpha$ and IL-6 at the mRNA levels without an appreciable cytotoxic effect on RAW 264.7 macrophag cells. Furthermore, PCM inhibited LPS-induced nuclear factor-kappa B (NF-$\kappa$B) activation as determined by NF-$\kappa$B reporter gene assay, and this inhibition was associated with a decrease in the nuclear translocation of p65 and p50 NF-$\kappa$B. Taken together, these results suggest that PCM may play an anti-inflammatory role in LPS-stimulated RAW 264.7 macrophages through the inhibitory regulation of iNOS, COX-2, TNF-$\alpha$ and IL-6 via NF-$\kappa$B inactivation.

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.525-531
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• 2014

In the present study, we investigated whether apigenin significantly affects tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced production and gene expression of MUC5AC mucin in airway epithelial cells. Confluent NCI-H292 cells were pretreated with apigenin for 30 min and then stimulated with TNF-${\alpha}$ for 24 h or the indicated periods. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Apigenin significantly inhibited MUC5AC mucin production and down-regulated MUC5AC gene expression induced by TNF-${\alpha}$ in NCI-H292 cells. To elucidate the action mechanism of apigenin, effect of apigenin on TNF-${\alpha}$-induced nuclear factor kappa B (NF-${\kappa}B$) signaling pathway was also investigated by western blot analysis. Apigenin inhibited NF-${\kappa}B$ activation induced by TNF-${\alpha}$. Inhibition of inhibitory kappa B kinase (IKK) by apigenin led to the suppression of inhibitory kappa B alpha ($I{\kappa}B{\alpha}$) phosphorylation and degradation, p65 nuclear translocation. This, in turn, led to the down-regulation of MUC5AC protein production in NCI-H292 cells. Apigenin also has an influence on upstream signaling of IKK because it inhibited the expression of adaptor protein, receptor interacting protein 1 (RIP1). These results suggest that apigenin can regulate the production and gene expression of mucin through regulating NF-${\kappa}B$ signaling pathway in airway epithelial cells.

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.202-210
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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 flower (ADF) 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. 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 ADF 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 flower extract has potential therapeutic benefits against various inflammatory diseases.