• Journal of Life Science
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• v.23 no.8
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• pp.984-988
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• 2013

Sparassis crispa is an edible mushroom with medicinal properties that contains more than 40% ${\beta}$-glucan. The role of S. crispa in regulating the functional activation of macrophages has yet to be fully elucidated. The objective of this study was to investigate the molecular mechanism underlying the immune-stimulatory function of S. crispa soluble ${\beta}$-glucan and extracts on macrophages. In this study, we showed that S. crispa soluble ${\beta}$-glucan was able to stimulate TNF-${\alpha}$ and IL-$1{\beta}$ production through NF-${\kappa}B$ activation in Raw 264.7 cells. We also showed that S. crispa extracts could not only enhance TNF-${\alpha}$ production in Raw 264.7 cells, but also suppress tumor growth in vivo. All of our results suggest that S. crispa could be developed as a promising immunostimulatory principle, applicable to cancer patients.

• Parasites, Hosts and Diseases
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• v.47 no.3
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• pp.205-212
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• 2009

Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis Iysates increased proinflammatory cytokines, such as TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by HMDM. The involvement of nuclear factor (NF)-${\kappa}B$ signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-${\kappa}B$. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-${\kappa}B$ activation and TNF-${\alpha}$ production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-${\kappa}B$ inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-${\alpha}$. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-${\alpha}$, and NO. In particular, we showed that T. vaginalis induced TNF-${\alpha}$ production in macrophages through NO-dependent activation of NF-${\kappa}B$, which might be closely involved in inflammation caused by T. vaginalis.

• Journal of Marine Bioscience and Biotechnology
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• v.12 no.2
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• pp.99-107
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• 2020

Osteoarthritis (OA) is an inflammatory degenerative joint disease that is accompanied by irreversible joint cartilage destruction. Recently, the antioxidant effects of Carpomitra costata, which is a type of brown algae, have been reported, but their effects on OA have not been investigated. In this study, the anti-osteoarthritic effect of the ethanol extract of C. costata (EECC) on SW1353 human chondrocytes was studied. Results showed that EECC significantly attenuated the interleukin-1β (IL-1β)-induced release of pro-inflammatory mediators, including prostaglandin E2 and nitric oxide (NO), as well as expressions of cyclo-oxygenase-2 and inducible NO synthase. EECC also inhibited the IL-1β-induced expressions of matrix metalloproteinase-1, -3, and -13 in SW1353 chondrocytes, which reduced their extracellular secretion. In addition, the oxidative stress induced by IL-1β was confirmed to be blocked by EECC due to the inhibition of reactive oxygen species generation. Moreover, EECC suppressed IL-1β-mediated translocation of nuclear factor-kappa B (NF-κB) from cytosol into the nucleus and the degradation of IκB-α, which indicates that EECC exhibits anti-inflammatory effects by inhibiting the NF-κB signaling pathway. These results are the first to demonstrate the anti-inflammatory activities of C. costata extracts in chondrocytes, thus suggesting that this algae extract may be used in the treatment of OA.

• Journal of Applied Biological Chemistry
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• v.56 no.4
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• pp.249-255
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• 2013

Recently, algae has been considered as a potential anti-inflammatory source due to its distinctive habitat environment exposing to light and high oxygen concentration. In present study, anti-inflammatory effect of brown alga, Sargassum fullvellum ethanol extract (SFEE), was examined. SFEE inhibited not only the production of nitric oxide and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) but also the expression of inducible nitric oxide synthase and cyclooxygenase 2 in LPS-induced RAW 264.7 cells without affecting cell viability. SFEE also suppressed the expression of nuclear factor kappa B (NF-${\kappa}B$), suggesting that SFEE could affect the expression of inflammation related cytokines and proteins through the regulation of NF-${\kappa}B$. Furthermore, formation of edema of the ear was 40% lower in mice treated with the highest dose (250 mg/kg) of SFEE than in the control mice. Thus, our study showed that SFEE may be a potential therapeutic anti-inflammatory drug.

• Molecules and Cells
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• v.26 no.2
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• pp.175-180
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• 2008

$I{\kappa}B$ kinase (IKK), the pivotal kinase in signal-dependent activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), is composed of multiple protein components, including IKK ${\alpha}/{\beta}/{\gamma}$ core subunits. To investigate the regulation of the IKK complex, we immunoaffinity purified the IKK complex, and by MALDI-TOF mass spectrometry identified a splice variant of zinc finger protein 268 (ZNF268) as a novel IKKinteracting protein. Both the full-length and the spliced form of the ZNF268 protein were detected in a variety of mammalian tissues and cell lines. The genes were cloned and expressed by in vitro transcription/translation. Several deletion derivatives, such as KRAB domain (KRAB) on its own, the KRAB/spacer/4-zinc fingers (zF4), and the spacer/4-zinc fingers (zS4), were ectopically expressed in mammalian cells and exhibited had different subcellular locations. The KRAB-containing mutants were restricted to the nucleus, while zS4 was localized in the cytosol. TNF-${\alpha}$-induced NF-${\kappa}B$ activation was examined using these mutants and only zS4 was found to stimulate activation. Collectively, the results indicate that a spliced form of ZNF268 lacking the KRAB domain is located in the cytosol, where it seems to play a role in TNF-${\alpha}$-induced NF-${\kappa}B$ activation by interacting with the IKK complex.

• The Korea Journal of Herbology
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• v.32 no.2
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• pp.25-32
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• 2017

Objectives : This study was conducted to investigate candidate materials as anti-inflammatory agent from extracts of Korean medicinal plants in Hwaak mountain. Ligustrum obtusifolium (LO) is a Korea medicinal plants that commonly used for robustness and hemostasis. It has been reported that LO has exhibited anti-ischemic, anti-oxidative, anti-hypolipidemic, anti-tumor and hypoglycemic effects. However, LO has not been previously reported to have an anti-inflammatory effect. Therefore, we have evaluated the anti-inflammatory effects of LO and its underlying molecular mechanisms in LPS-induced RAW 264.7 macrophages. Methods : Cell viability was determined by MTT assay in RAW 264.7 macrophages. Nitric Oxide (NO) was measured with Griess reagent and pro-inflammatory cytokines were detected by ELISA in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and p65 subunit of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) were determined by Western blot analysis. Results : Among 15 extracts of Korean medicinal plants tested, Ligustrum obtusifolium (LO) showed the inhibition of NO production without cytotoxicity. LO reduced the expression levels of iNOS and COX-2 proteins in LPS-simulated RAW 264.7 macrophages in dose-dependent manner. Consistent with these data, LO inhibited the productions of $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$ in LPS-simulated RAW 264.7 macrophages. Furthermore, LO attenuated the LPS-induced nuclear translocation of p65 $NF-{\kappa}B$ in RAW 264.7 macrophages involving suppression of $NF-{\kappa}B$ activation. Conclusions : Taken together, these results suggest that the anti-inflammatory effects of LO is associated with regulation of inflammatory mediators via inhibition of $NF-{\kappa}B$ activation in LPS-treated RAW 264.7 macrophages.

• Nutrition Research and Practice
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• v.14 no.6
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• pp.593-605
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• 2020

BACKGROUND/OBJECTIVES: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (Aβ) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against Aβ-induced neuroinflammation and the underlying mechanism in C6 glial cells. MATERIALS/METHODS: C6 glial cells were treated with PF and Aβ_25-35, and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and Aβ degradation was determined by Western blot. RESULTS: Aβ_25-35 significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited Aβ_25-35-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-κB) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-κB was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of Aβ degrading enzymes, insulin degrading enzyme and neprilysin. CONCLUSIONS: These findings indicate that PF exerts protective effects against Aβ-mediated neuroinflammation by inhibiting NF-κB signaling, and these effects were associated with the enhanced activity of Aβ degradation enzymes.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.45-49
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• 2005

Background: Inflammation in the brain has known to be associated with the development of a various neurological diseases. The hallmark of neuro-inflammation is the activation of microglia, brain macrophage. Pro-inflammatory compounds including nitric oxide (NO) are the main cause of neuro-degenerative disease such as Alzheimer's disease (AD) which is resulted in cell death. Among those pro-inflammatory compounds, NO contributes to the cell death by directly or indirectly. Methods: In the study, we examined whether ursodeoxycholic acid (UDCA), a non-toxic hydrophilic bile acid, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS). In signal transduction, we also examined the NF-${\kappa}B$ (p65/p50), IKK, and I ${\kappa}B$, which are associated with the expression of iNOS gene using western blots. Results: In the present study, we found that UDCA effectively inhibited NO production in BV-2 microglial cell, and NF-${\kappa}B$ activation was reduced by suppressing IKK gene expression and by increasing the I${\kappa}B$ in cytosol comparing those to the positive control LPS. Conclusion: Taken together, these data suggested that UDCA may playa crucial role in inhibiting the NO production and the results imply that UDCA suppresses a cue signal of the microglial activation via stimulators, such as ${\beta}$-amyloid peptides which are known to stimulate microglia in AD pathogenesis.

• BMB Reports
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• v.52 no.6
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• pp.409-414
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• 2019

Natural compounds isolated from medicinal herbs and plants have immense significance in maintaining bone health. Hydrolysable tannins have been shown to possess a variety of medicinal properties including antiviral, anticancer, and anti-osteoclastogenic activities. As a part of a study on the discovery of alternative agent against skeletal diseases, we isolated a hydrolysable tannin, 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-${\beta}$-D-glucose (DTOGG), from Galla Rhois and examined the effect on osteoclast formation and function. We found that DTOGG significantly inhibited receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation by downregulating the expression of the key regulator in osteoclastogenesis as well as osteoclast-related genes. Analysis of RANKL/RANK signaling revealed that DTOGG impaired activation of $I{\kappa}B{\alpha}$ and p65 in the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-${\kappa}B$) signaling pathway. Furthermore, DTOGG reduced bone resorbing activity of osteoclasts, compared to the vehicle-treated control. These results suggest that DTOGG could be a useful natural compound to manage osteoclast-mediated skeletal diseases.

• Journal of Life Science
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• v.21 no.11
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• pp.1636-1640
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• 2011

Alzheimer's disease (AD) is a progressive neurodegenerative disease, resulting in the loss of cognitive function. Mitochondrial aldehyde dehydrogenase (ALDH2) has been proposed to be a risk factor for the development of AD, but there is still controversy about that. In this study, we demonstrated the role of ALDH2 enzyme activity on amyloid-beta (A${\beta}$) and nuclear factor kappa B (NF-${\kappa}B$) expression in mice brain following ethanol exposure for 8 weeks. Five male Aldh2 (+/+) and Aldh2 (-/-) mice, 8 weeks-old of age (C57BL/6J strain), in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage. Those in the control groups received 0.9% saline alone. Results showed a difference in expression level of A${\beta}$ in the hippocampus after ethanol exposure according to the ALDH2 enzyme activity (p<0.05), but not in the level of NF-${\kappa}B$). Our results suggest a possibility that ALDH2 enzyme activity may be an important role in the development of AD.