• YAKHAK HOEJI
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• v.56 no.1
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• pp.20-25
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• 2012

In Northeast Asia, Paeoniae Radix has been used in treatments of inflammation-causing diseases such as arthritis for many centuries. Paeoniflorin, one of the principle bioactive monoterpene glucosides from the paeony root, is reported to be mostly responsible for the effectiveness of the treatments. However, the anti-inflammatory effect of a monoterpene, paeoniflorigenone (PFG) which partially has the moiety of paeoniflorin minus a glucose structure is unknown. Thus, the aim of this work was to investigate anti-inflammatory activity of PFG. For the investigation, PFG activity on the NO (nitric oxide) production from LPS-stimulated macrophages, and the anti-inflammatory effect was tested in the animal model of septic arthritis caused by Candida albicans, a major etiological agent for septic arthritis. For induction of the arthritis, mice were administered with an emulsion of C. albicans cell wall (CACW) mixed with Complete Freund's Adjuvant (CFA) via footpad-injection (Day 0); PFG at a dose of 0.5 or 1 mg/mouse (25 or 50 mg/kg of body-weight) was given to the animals on Day 3, 6, and 9; footpads were scored for arthritis. Moreover, the PFG effect on proliferation of T-lymphocyte that causes aggravation of arthritis was additionally tested. Data resulting from those tests showed that PFG inhibited the NO production from the stimulated macrophage in a dose dependent manner (P<0.05), indicating that PFG is an anti-inflammatory. To confirm the in-vitro results, anti-inflammatory activity of PFG was determined against C. albicans-caused septic arthritis. Data showed that PFG-treatment reduced footpad-swelling which indicates that PFG has anti-arthritic effect (P<0.05), which is therapeutic. The anti-arthritic effect appeared to be mediated by PFG suppression of T-cell proliferation. Ultimately, PFG, a monoterpene component, has anti-inflammatory activity analogous to paeoniflorin. The anti-inflammatory activity treats the septic arthritis due to a pathogenic fungus C. albicans.

• Toxicological Research
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• v.33 no.4
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• pp.283-290
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• 2017

The host immune system is the first line of host defense, consisting mainly of innate and adaptive immunity. Immunity must be maintained, orchestrated, and harmonized, since overactivation of immune responses can lead to inflammation and autoimmune diseases, while immune deficiency can lead to infectious diseases. We investigated the regulation of innate and adaptive immune cell activation by Artemisia capillaris and its components (ursolic acid, hyperoside, scopoletin, and scopolin). Macrophage phagocytic activity was determined using fluorescently labeled Escherichia coli, as an indicator of innate immune activation. Concanavalin A (ConA)- and lipopolysaccharide (LPS)-induced splenocyte proliferation was analyzed as surrogate markers for cellular and humoral adaptive immunity, respectively. Neither A. capillaris water extract (WAC) nor ethanol extract (EAC) greatly inhibited macrophage phagocytic activity. In contrast, WAC suppressed ConA- and LPS-induced proliferation of primary mouse splenocytes in a dose-dependent manner. Similarly, EAC inhibited ConA- and LPS-induced splenocyte proliferation. Oral administration of WAC in mice decreased ConA- and LPS-induced splenocyte proliferation, while that of EAC suppressed LPS-induced splenocyte proliferation. Repeated administration of WAC in mice inhibited ConA- and LPS-induced splenocyte proliferation. Ursolic acid, scopoletin, and scopolin reduced ConA- and LPS-induced primary mouse splenocyte proliferation, while hyperoside did not show such activity. These results indicate that A. capillaris and its components, ursolic acid, scopoletin, and scopolin, suppress ConA- and LPS-induced adaptive immune cell activation. The results suggest that A. capillaris is useful as a regulator of adaptive immunity for diseases involving excessive immune response activation.

• Nutrition Research and Practice
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• v.2 no.2
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• pp.134-137
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• 2008

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCLl5), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions playa crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCLl5 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis.

• Journal of Oral Medicine and Pain
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• v.31 no.1
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• pp.17-25
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• 2006

The present study was undertaken to determine the possible cellular mechanism of action of angiopoietin-2 in bone metabolism. The effects on the osteoblasts were determined by measuring 1) cell viability, 2) alkaline phosphatase (ALP) activity, 3) gelatinase activity, and 4) nitric oxide production. The effects on the osteoclasts were investigated by measuring 1) tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells (MNCs) formation, and 2) resorption areas after culturing osteoclast precursors. Angiopoietin-2 treatment showed a significant increase in both the viability and ALP activity of osteoblasts. Angiopoietin-2 increased the activity of gelatinase and nitric oxide production. In addition, angiopoietin-2 decreased the osteoclast generation induced by macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL), and inhibited osteoclastic activity in (M-CSF)-dependent bone marrow macrophage (MDBM) cell cultures. Taken these results, angiopoietin-2 may be a regulatory protein within the bone marrow microenvironment.

• YAKHAK HOEJI
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• v.42 no.1
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• pp.82-88
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• 1998

The effect of hepatoprotective agents and bile acids on tumor necrosis factor-alpha, (TNF-${\alpha}$) production in murine and human macrophage cell line (RAW264.7 and U937) was inve stigated. The hepatoprotective agents including silymarin and its major component, silybin, significantly inhibited TNF-alpha production in a concentration dependent manner ($IC_50$ of silybin=67.7${\mu}g$/ml (140.3${\mu}g$M)). In differentiated U937 cells, especially, silybin showed more effective inbitory activity ($IC_50$=35.1${\mu}g$g/ml (72.7${\mu}g$M)). These results suggest that silymarin and silybin may inhibit TNF-alpha production in the process of hepatic diseases in human. However, biphenyldimethyl dicarboxylate (DDB) was not effective. In the case of bile acids, chenodeoxycholic acid (CDCA) showed a concentration dependent inhibitory effect on TNF-alpha production ($IC_50$ of CDCA= 71.5${\mu}g$g/ml (182.1${\mu}g$M)). In contrast, glycine or taurine conjugated form (G-CDCA or T-CDCA) restored to the control level or significantly increased TNF-${\alpha}$ production. And also ursodeoxycholic acid (UDCA) and its conjugated forms (G-UDCA and T-UDCA) showed a variety of patterns on TNF-${\alpha}$ production by changes of functional groups and concentration. These results also indicate that bile acids may regulate TNF-${\alpha}$ production in normal hepatic function or disease conditions.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.61-67
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• 2014

Objectives : Aconiti Lateralis Preparata Radix (Aconitum Carmichaeli, AC) and Cinnamomi Cortex (Cinnamomi Cortex, CC) have been treated to elderly for kidney yang enhancement in Korean traditional medicine. In this study, the effects of water extract of AC and CC on RANKL (Receptor Activator for Nuclear Factor ${\kappa}B$ Ligand)-induced osteoclast differentiation were evaluated in culture system. Methods : MTT assay was used to evaluate the potential cytotoxicity of AC and CC extracts in bone macrophage marrows (BMMs) stimulated with M-CSF. TRAP (tartrate-resistant acid phosphatase) staining and TRAP activity were performed to know the inhibitory effect on osteoclast differentiation. The protein expression levels of nuclear factors such as activated T cell(NFAT)c1, c-Fos, MAPKs and ${\beta}$-actin in cell lysates treated with AC and CC extracts were analysed by western blotting. Results : AC, CC extracts and their co-administration inhibited significantly RANKL-induced osteoclast differentiation in BMMs in a dose dependent manner without toxicity. Each AC and CC extracts inhibited the phosphorylation of p38. Also, AC and CC extracts, respectively, inhibited the protein expression of c-Fos and NFATc1 more than Co-administration of AC and CC even if all treatments did. It was observed that RANKL-induced degradation of I-${\kappa}B$ is significantly suppressed by all treatments. Conclusions : Taken together, It was concluded that AC and CC have beneficial effect on osteoporosis by inhibition of osteoclast differentiation. Thus, Atractylodis AC and CC could be a treatment option for osteoporosis.

• The Korea Journal of Herbology
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• v.37 no.5
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• pp.53-61
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• 2022

Objectives : The aim of this study was to investigate the effect of Baicalein (BA) on the production of hydrogen peroxide in lipoteichoic acid-stimulated RAW 264.7 mouse macrophages. Methods : Lipoteichoic acid-stressed RAW 264.7 mouse macrophages were incubated with baicalein at concentrations of 50 and 100 µM. Incubation time is 30 minutes, 2 h, 12 h, and 18 h. After incubation, The production of hydrogen peroxide in RAW 264.7 mouse macrophages was measured with dihydrorhodamine 123 assay. Streptococcus aureus lipoteichoic acid and Streptococcus pyogenes lipoteichoic acid were used as cell-stimulating lipoteichoic acid. Cell viabilities were measured with a modified MTT assay. Berberine, indomethacin, and gallic acid were incubated for the same time as the comparative materials. Results : BA at the concentration of 50 and 100 µM did not show cytotoxicity on RAW 264.7 mouse macrophages for 24 h incubation. For 30 minutes, 2 h, 12 h, and 18 h incubation, BA at the concentration of 50 and 100 µM significantly inhibited the production of hydrogen peroxide in RAW 264.7 mouse macrophages stimulated by Streptococcus aureus lipoteichoic acid (p < 0.05); also, BA at the concentration of 50 and 100 µM also inhibited the productions of hydrogen peroxide in RAW 264.7 mouse macrophages stimulated by Streptococcus pyogenes lipoteichoic acid significantly (p < 0.05). Conclusions : BA might have anti-bacterial activity related to its inhibition of hydrogen peroxide production in lipoteichoic acid-stimulated RAW 264.7 mouse macrophages.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.52-52
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• 2003

Granulocyte-macrophage colony stimulating factor (GM-CSF) is synthesized in the female reproductive tract and has been shown to play an important role in human and murine embryo development and implantation. However, the mechanism of GM-CSF on the embryo development is unknown. Recent studies suggested that GM-CSF may be increase the expression of implantation relented genes, such as interleukin-1 (IL-1) system. Our aim of this study was to compare the interleukin-1$\alpha$ (IL-1$\alpha$), interleukin-1$\beta$ (IL-1$\beta$) and interleukin-1 receptor antagonist (IL-lra) mRNA between the GM-CSF supplemented group and control group in mouse embryos. Mouse 2-cell embryos were cultured in P-1 medium supplemented with or without mouse GM-CSF (10 ng/ml). The number of total and apoptotic cell in blastocyst were assessed by TUNEL. And then, the expression of IL-1$\alpha$, IL-1$\beta$ and IL-1ra mRNA in blastocyst were examined by RT-PCR.

• Journal of Yeungnam Medical Science
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• v.41 no.2
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• pp.103-112
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• 2024

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8⁺ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.1
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• pp.26-31
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• 2011

Purpose: Chronic inflammatory gingival lesions occur as pyogenic granulomas or non-specific chronic suppurative lesions. Methods: Of the 59 chronic inflammatory gingival lesions examined, plasma cell granuloma (n=14), which showed an intense antibody-mediated immune reaction with the increased infiltration of plasma cells, was observed as a pseudotumor-like gingival overgrowth and myofibroblastic or fibrohistiocytitc proliferation of stromal cells with a heavy collection of plasma cells. The levels of CD3, CD20, CD31, CD68, RANKL, cathepsin G, cathepsin K, lysozyme, TNF${\alpha}$, MMP-2, and MMP-9 in the 14 cases of gingival plasma cell granuloma with immunohistochemical detection were measured to determine the pathogenetic progresses of the plasma cell granuloma compared to the common pyogenic granuloma (n=45) in the gingiva. Results: The gingival lesions of the plasma cell granuloma could be divided into three histological types, plasma cell predominant type (PPT, n=8), mixed inflammatory cell type (MICT, n=2), and sclerosed fibrosis type (SFT, n=4). The PPT showed a condensed infiltration of plasma cells into the perivascular spaces of the granulomatous lesion with frequent formation of Russel's body in their cytoplasm. The MICT showed the concomitant infiltration of many macrophages together with plasma cells, resulting in the diffuse destruction of stromal fibrous tissue. The SFT showed granulomatous lesions replaced gradually by thick collagenous fibrous tissue, resembling an inflammatory pseudotumor. The SFT expressed strongly the lymphocytic markers, CD3 and CD20, and the macrophage/monocyte markers, CD31 and CD68, but showed reduced expression of common inflammatory markers, TNF${\alpha}$, cathepsin G, lysozyme, MMP-2, and MMP-9, as well as the reduced expression of osteoclastogenic markers, RANKL and cathepsin K. Conclusion: These results suggest that a gingival plasma cell granuloma shows variable gene expression for cell-mediated immunity and stromal tissue degeneration, undergoing sclerotic fibrosis with a persistent inflammatory reaction.