• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1179-1185
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• 2004

The Korean traditional medicine, Seonghyangjeonggisan (SHJGS) has long been used for acute cerebral infarction (Cl). However, scientific investigation has been carried out a little. Cytokines, involved in the regulation of inflammatory reactions and immune responses, may play an important role in the pathogenesis of Cl. The aim of this study is to investigate the effects of SHJGS on the production of various cytokines in the patients with acute Cl. Peripheral blood mononuclear cells (PBMC) obtained from the patients with acute Cl were cultured for 24hr in the presence or absence of lipopolysaccharide (LPS) and phytohaemagglutinin (PHA). The amount of TNF-α, IL-1β, IL-6 and IL-8, in PBMC culture supernatant, was significantly increased in the LPS and PHA treated cells, compared with unstimulated cells (P<0.05). This study showed that increased TNF-α, IL-1β, IL-6 and IL-8 level stimulated by LPS and PHA was inhibited by SHJGS (0.01-1 ㎎/㎖) in a dose-dependent manner but IL-8 level was not inhibited significantly at 1㎎/㎖ (P>0.05). The maximal inhibition rate of TNF-α, IL-1β, IL-6 and IL-8 by SHJGS (1㎎/㎖) was 68% (P<0.05), 53.9% (P<0.05), 45.5% (P<0.05), 46.7% (P>0.05) respectively. These results suggest that SHJGS might have anti-inflammatory effects through cytokine modulation. which might explain its beneficial effects in the treatment of acute Cl.

• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

• The Korean Journal of Food And Nutrition
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• v.36 no.6
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• pp.535-542
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• 2023

We investigated the anti-inflammatory effects of shiitake mushroom and kelp (SMK) mixture extracts in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 cells. Treatment of RAW 264.7 cells with LPS significantly increased NO (nitric oxide) production, pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and IL-1β), and inflammation-related genes (COX-2 and inducible nitric oxide synthase (iNOS)). In cytotoxicity testing using RAW 264.7 cells, SMK mixture extracts in the range of 1-16 ㎍/mL did not inhibit cell proliferation. However, SMK mixture extracts significantly inhibited NO production in a dose-dependent manner (p<0.05). SMK treatment significantly decreased TNF-α, IL-6, IFN-γ, and IL-1β levels compared to the LPS group, and similarly, pro-inflammatory cytokine mRNA levels also decreased. SMK mixture extracts reduced the mRNA expression of COX-2 and iNOS in RAW 264.7 cells compared to LPS (p<0.05). The above results show that SMK mixture extracts suppressed the inflammatory response induced by LPS. In particular, the extracts were shown to regulate the inflammatory response by suppressing the expression of inflammatory cytokines and inflammation-related enzymes.

• Journal of Yeungnam Medical Science
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• v.38 no.4
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• pp.326-336
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• 2021

Background: Sulfation of heparan sulfate proteoglycans (HSPGs) is critical for the binding and signaling of ligands that mediate inflammation. Extracellular 6-O-endosulfatases regulate posttranslational sulfation levels and patterns of HSPGs. In this study, extracellular 6-O-endosulfatases, sulfatase (Sulf)-1 and Sulf-2, were evaluated for their expression and function in inflammatory cells and tissues. Methods: Harvested human peripheral blood mononuclear cells were treated with phytohemagglutinin and lipopolysaccharide, and murine peritoneal macrophages were stimulated with interleukin (IL)-1β for the evaluation of Sulf-1 and Sulf-2 expression. Sulf expression in inflammatory cells was examined in the human rheumatoid arthritis (RA) synovium by immunofluorescence staining. The antigen presentation and phagocytic activities of macrophages were compared according to the expression state of Sulfs. Sulfs-knockdown macrophages and Sulfs-overexpressing macrophages were generated using small interfering RNAs and pcDNA3.1 plasmids for Sulf-1 and Sulf-2, respectively. Results: Lymphocytes and monocytes showed weak Sulf expression, which remained unaffected by IL-1β. However, peritoneal macrophages showed increased expression of Sulfs upon stimulation with IL-1β. In human RA synovium, two-colored double immunofluorescent staining of Sulfs and CD68 revealed active upregulation of Sulfs in macrophages of inflamed tissues, but not in lymphocytes of lymphoid follicles. Macrophages are professional antigen-presenting cells. The antigen presentation and phagocytic activities of macrophages were dependent on the level of Sulf expression, suppressed in Sulfs-knockdown macrophages, and enhanced in Sulfs-overexpressing macrophages. Conclusion: The results demonstrate that upregulation of Sulfs in macrophages occurs in response to inflammation, and Sulfs actively regulate the antigen presentation and phagocytic activities of macrophages as novel immune regulators.

• The Korea Journal of Herbology
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• v.35 no.4
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• pp.37-43
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• 2020

Objectives : Allium hookeri is a well-known traditional herbal remedy and its root used for treatment of inflammation and tumor. However, the mechanism of anti-inflammatory effect of Allium hookeri is still unknown. This study aims to examine the mechanism of anti-inflammatory effect of Allium hookeri on mouse macrophage cell line, RAW 264.7 cells. Methods : Anti-oxidant effect of water extract of Allium hookeri (WEAH) was measured by 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay. 3- (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was performed to determine the effect of WEAH on cell viability in RAW 264.7 cells. In addition, anti-inflammatory effect of WEAH was investigated in RAW 264.7 cells. Inflammation of RAW 264.7 cells induced by lipopolysarccharide (LPS) treatment and expression levels of inflammatory cytokine interleukin 1 β (IL-1β) and interleukin 6 (IL-6) gene were analyzed using quantitative reverse transcription PCR (qRT-PCR) analysis. Furthermore, the phosphorylation of inhibitor of nuclear factor kappa B (IκBα) after LPS treatment with WEAH-treated RAW 264.7 cells was confirmed by immunoblot analysis. Results : WEAH showed a strong anti-oxidant effect and no cytotoxicity to RAW 264.7 cells up to 2 mg/㎖ concentration. The LPS-induced mRNA expression levels of IL-1β and IL-6 were decreased by WEAH treatment. Furthermore, the LPS-induced phosphorylation of IκBα is attenuated by WEAH treatment. Conclusions : Through experimental demonstration of anti-oxidant and anti-inflammatory effects of WEAH, we suggest that Allium hookeri is a valuable material for prevention and treatment of various inflammatory diseases.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.54 no.4
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• pp.552-560
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• 2021

This study investigated anti-inflammatory and antibacterial activities of Sedum takesimense ethanolic extract, and 3 isolated compounds. To confirm anti-inflammatory and anti-acne activities, a nitric oxide (NO) inhibition assay, pro-inflammatory factor (TNF-α, IL-1β, and IL-8) inhibition assays, and minimum inhibitory concentration (MIC) tests were performed. The 3 isolated compounds were identified as 4,6-di-O-galloylarbutin (OGA), 2,4,6-tri-O-galloyl-glucose (OGG), and 1,2,4,6-tetra-O-galloyl-β-glucose (TOGG). The ethanolic extract and isolated compounds (OGA, OGG, TOGG) effectively inhibited production of NO and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-8). Furthermore, OGG and TOGG exhibited MIC values toward Cutibacterium acnes of 12.5 ㎍/mL and 3.2 ㎍/mL, respectively. These results suggest that S. takesimense extract exerts an anti-inflammatory effect on LPS-induced RAW264.7 cells, and an antibacterial efficacy against C. acnes.

• Korean Journal of Pharmacognosy
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• v.52 no.3
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• pp.192-201
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• 2021

Dangguisu-san (DGSS) is widely known traditional herbal medicinal formula in Korea for treatment of traumatic injury by traffic accident, ecchymosis, abdominal distension and anti-thrombosis of blood. This study was conducted to develop the simultaneous analyze method using high performance liquid chromatography (HPLC) and examine the effect of anti-inflammatory activity of DGSS-dry extract (DGSS-DE) and DGSS-mix extract powder (DGSS-MEP). Physicochemical characteristics of DGSS-DE and DGSS-MEP showed that there is no significant difference in pH, titratable acidity, total soluble solid content and browning degree except for color value (L, a, b). 15 functional constituents of DGSS were identified and the correlation coefficient values of DGSS-DE and DGSS-MEP were conformed 0.950. Also, DGSS-DE and DGSS-MEP significantly decreased the secretion of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) through inhibited expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, IL-6, and TNF-α. From these result, DGSS-MEP showed similar chemical composition and anti-inflammatory effect to DGSS-DE. Therefore, DGSS-DE and DGSS-MEP may be useful as potential source of drug to prevent inflammation.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.395-401
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• 2021

Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E₂ (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.

• Journal of Preventive Veterinary Medicine
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• v.43 no.4
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• pp.214-220
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• 2019

Although canine brucellosis has been known to be an important re-emerging zoonosis, the pathophysiological mechanisms of Brucella canis infection remains clues to be solved. Different culture models, single and co-culture models, were constructed with canine epithelial cells, D17 and macrophage, DH82 to investigate the induction of immune responses in in vivo B. canis infection. Expression of genes related with induction of immune responses, Th1, Th2 and Th17, was compared in the two different models after the bacterial infection. In this study, expression of cytokine genes, IL-1β, IL-5, IL-6, IL-10, IL-23, and TNF-α was quantified in the DH82 at different time points using RT-qPCR in the two different culture systems after the infection. Cytokine genes related with Th1, IL-1β and TNF-α and Th17, IL-6 and IL-23 were expressed with time-dependent manners in the both systems (p<0.05). However, increase of Th2-related cytokine genes expression was not detectable in the both systems by comparison with control. The expression of Th1 and Th17 related cytokine genes was earlier in single cell culture than those in co-culture model (p<0.05). In general, amounts of the expressed genes were shown higher in single cell model than those in co-culture models. This study indicate that Th1 and Th17-associated immune responses are central to B. canis infection in dogs. In addition, it suggests a specific role of epithelial cells in the B. canis infection in vivo, which should resolved in the further study.

• Bulletin of the Korean Chemical Society
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• v.14 no.1
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• pp.5-9
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• 1993