• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.210-217
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• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.31 no.4
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• pp.1-12
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• 2018

Objectives : This study investigated the anti-oxidant and anti-inflammatory activities of Changchulgeumryeontang (CCGRT) extract. Methods : The macrophage cell line RAW 264.7 cells were used and MTT assay was performed to measure the cell viabilities at the various concentrations of CCGRT ($25-200{\mu}g/m{\ell}$). Nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) were measured in LPS-induced RAW 264.7 cells. Expressions of iNOS, $NF-{\kappa}B$, $IL-1{\alpha}$, $IL-1{\beta}$ and IL-6 were also performed by real-time PCR. The anti-oxidant activities of CCGRT was measured by DPPH radical scavenging activity. Results : 1. there was no cytotoxicity in RAW264.7 cells treated with CCGRT compared to the control. 2. CCGRT treated group significantly inhibited NO and $PGE_2$ production compared to the LPS treated group. 3. CCGRT treated group significantly decreased mRNA expressions of iNOS, $NF-{\kappa}B$, $IL-1{\alpha}$, $IL-1{\beta}$ and IL-6 compared to the LPS treated group. 4. CCGTR was found to have high DPPH free radical scavenging ability. Conclusions : According to the above results, CCGRT may be a potentional choice for the treatment of inflammatory skin disease. Conclusions : According to the above results, CCGRT may be a potentional choice for the treatment of inflammatory skin disease.

• Journal of Haehwa Medicine
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• v.15 no.2
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• pp.105-119
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• 2006

This study aimed to investigate the effects of Sesami Semen on the itching and anti-allergic inflammation mechanism related with cytokine, chemokine, histamine, $\beta$-hexosaminidase, NF-$\kappa$B, and free radical, and it was concluded as follows : 1. Sesami Semen did not show any cytotoxicity at the range of con-centration (1-250 ${\mu}g/m\ell$) on the human fibroblast cell (hFCs). 2. Sesami Semen reduced the gene expressions of IL-8, TNF-$\alpha$, IL-6 mRNA comparing with control. 3. Sesami Semen reduced the levels of IL-6, IL-8, MCP-1 within THP-1 cell depending on the concentration, and especially significantly reduced the the levels of IL-6, MCP-1 at all the concentration. 4. Sesami Semen significantly decreased the histamine secretion on HMC-1 at all the concentration. 5. Sesami Semen decreased the $\beta$-Hexosaminidase secretion 6.2% at 10 ${\mu}g$/ml conc., 58.3% at 100 ${\mu}g$/ml conc. and 63.2% at 200 ${\mu}g$/ml conc., respectively. And IC50 (${\mu}g$/ml) was 158.25 ${\mu}g$/ml. 6. Sesami Semen significantly suppressed the activity of NF-$\kappa$B promoter depending on the concentration. 7. Sesami Semen decreased the production of reactive oxygen species (ROS) and DPPH generation depending on the concentration. As judged with above results, the effects of Sesami Semen on the anti-allergic inflamation would be recognized, and it could be applied on the medicinal sources for prevention or treatment of several allergy disease. And more studies are needed furthermore with the seperation of effective materials.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.46-58
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• 2005

Objective : This study on Sipimikwanjung-tang was undertaken to evaluate its antioxidant capacities and antiperoxidation activities in rat liver tissues. Sipimikwanjung-tang which has been one of the prescriptions in sasang constitutional medicine is usually applied for the therapy of various liver diseases. It is elucidated that Sipimikwanjung-tang has antioxidants on liver tissue of rat and the cytotoxic effects on human hepatoblastoma Hep G2 cells. Methods: Sipimikwanjung-tang extract in antioxidant effects of Hep G2 cells is evaluated by MTT assay, DAPI staining, DNA fragmentation assays and FACS can analysis. Results: Sipimikwanjung-tang induced apoptosis in Hep G2 cells, and induced G1 and G2M arrest of the cell cycle as well as a significant increase in PARP and caspase-3 activity. It induced an increase in $H_2O_2$ generation and the subsequent $NF-{\kappa}B$ activation and also induced cell apoptosis through the caspase-3-dependent pathways in the low concentration of Sipimikwanjung-tang extracts. However, the high dose of Sipimikwanjung-tang extract in Hep G2 cells inhibited $TGF-{\beta}l-induced$ apoptosis via increase in cellular $H_2O_2$, formation and $NF-{\kappa}B$ activation in human hepatoblastoma Hep G2 cells. Conclusion: From this study, the possibility that Sipimikwanjung-tang extracts apply to antioxidant and apoptotic treatment of disease is revealed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1320-1331
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• 2009

Oxidative stress and inflammation are important events in the development of chronic inflammatory diseases including arthritis, atherosclerosis, diabetes, hypertension. Cynomorium songaricum (CS) has been used as a traditional Korean herbal medicine, and it is currently used in traditional clinics to treat frequent urination, spermatorrhea, weakness of the sinews and constipation in the folk medicine. The aim of this study was to determine whether fractionated extracts of CS inhibit free radical generation such as DPPH radical, superoxide radical, nitric oxide and peroxynitrite, production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Cytotoxic activity of extracts on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. Our results indicated that the most superior extract which scavenged DPPH radical, reactive oxygen species (ROS) and RNS was CS ethyl acetate extract (CSEA). Moreover, CSEA significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-$\alpha$, IL-$1{\beta}$ and IL-6 formation in macrophages. Furthermore, CSEA treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$. These findings indicate that CSEA inhibits the production of pro-inflammatory mediators and cytokines via the suppression of ROS production and NF-${\kappa}B$ activation. Take together, these results indicate that CSEA has the potential for use as an natural anti-oxidant and an agent of anti-chronic inflammatory diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.47-54
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• 2019

Estrogen withdrawal in post-menopausal women leads to overactivation of osteoclasts, which contributes to the development of osteoporosis. Inflammatory cytokines are known as one of mechanisms of osteoclast activation after estrogen deficiency. SPA0355 is a thiourea derivative that has been investigated for its antioxidant and anti-inflammatory activities. However, its efficacy in bone resorption has not been previously investigated. The aim of this study was to investigate the impact of SPA0355 on the development of osteoporosis and to explore its mode of action. In vitro experiments showed that SPA0355 inhibited receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages. This effect appears to be independent of estrogen receptor activation as ICI 180,782 failed to abrogate its effects on osteoclasts. Further signaling studies revealed that SPA0355 suppressed activation of the MAPKs, Akt, and $NF-{\kappa}B$ pathways. SPA0355 also increased osteoblastic differentiation, as evidenced by its effects on alkaline phosphatase activity and mineralization nodule formation. Intraperitoneal administration of SPA0355 to ovariectomized mice prevented bone loss, as verified by three-dimensional images and bone morphometric parameters derived from ${\mu}CT$ analysis. Noticeably, SPA0355 did not show hepatotoxicity and nephrotoxicity and also had little effect on hematological parameters. Taken together, the results indicate that SPA0355 may protect against bone loss in ovariectomized mice by stimulation of osteoblast differentiation and by inhibition of osteoclast resorption. Therefore, SPA0355 is a safe and potential candidate for management of postmenopausal osteoporosis.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.63-70
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• 2019

Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.

• Korean Journal of Plant Resources
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• v.36 no.1
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• pp.15-25
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• 2023

Myriophyllum spicatum L. has been used as an ornamental in ponds and aquariums, and as a folk remedy for inflammation and pus. Nevertheless, the biological activity and underlying mechanisms of anti-inflammatory effects are unclear. This study is aimed at investigating the antioxidative and anti-inflammatory activities of ethanol extract of Myriophyllum spicatum L. (EMS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Antioxidant activity of EMS was assessed by radical-scavenging effects on ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. As inflammatory response parameters produced by LPS-stimulated RAW 264.7 cells were quantified to assess the anti-inflammatory activity of EMS. Our results showed that EMS increased FRAP and DPPH radical-scavenging activity. In EMS-treated RAW 264.7 cells, the production of NO, PGE₂, TNF-α and IL-1β was significantly inhibited at the non-cytotoxic concentration. In addition, EMS significantly attenuated LPS-stimulated the toll-like receptor (TLR) 4/myeloid differentiation protein (MyD) 88 signaling pathway, and inhibited nuclear translocation of nuclear factor-kappa B(NF-κB). Positive correlations were noted between anti-inflammatory activity and antioxidant activity. In conclusion, it was indicated that EMS suppresses the transcription of inflammatory factors by inhibiting the TLR4/MyD88/NF-κB signaling pathway, thereby suppressing LPS-stimulated inflammation in RAW 264.7 cells. This study highlights the potential role of EMS against inflammation and associated diseases.

• Journal of Applied Biological Chemistry
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• v.57 no.3
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• pp.227-234
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• 2014

The anti-inflammatory effect of Sargassum micracanthum water extract (SMWE) was investigated using lipopolysaccharide (LPS)-induced inflammatory response in this study. The murine macrophage cell line RAW 264.7 cells were used and MTT assay was performed to measure the cell proliferation ability. The secretion of nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and IL-$1{\beta}$ was measured in LPS-induced RAW 264.7 cells by ELISA. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear transcription factor-kappa B p65 protein was studied by immunoblotting. The Balb/c mice were used for an acute toxicity test, and imprinting control region mice were purchased to evaluate a croton oil-induced ear edema. As a result, there was no cytotoxicity in the macrophage proliferation treated with SMWE compared to the control. NO levels decreased with increasing concentration of SMWE and were inhibited over 50%. Moreover, the secretion of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed in a dose-dependent manner, especially, IL-$1{\beta}$ inhibition activity was over 50% at 50 ${mu}g$/mL. The formation of ear edema of mice was reduced at the highest dose tested compared to that in the control. Moreover, in acute toxicity test, no moralities occurred in mice administered 5,000 mg/kg body weight of SMWE over 2 weeks observation period. These results suggested that SMWE may have significant effects on inflammatory factors and be potential anti-inflammatory therapeutic materials.

• Food Science and Preservation
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• v.22 no.5
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• pp.735-743
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• 2015

This study investigated the anti-inflammatory activity of barley leaf extract in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and hairless mice. Pre-treatment with barley leaf extract significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-II (COX-II) in a dose-dependent manner in LPS-stimulated RAW264.7 cells. Barley leaf extract also significantly inhibited the secretion of inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) were strongly suppressed by barley leaf extract in LPS-stimulated cells. In hairless mice, barley extract significantly decreased the pathological phenotypes of contact dermatitis, such as erythema, edema, and scabs. These results indicate that barley leaf extract has an anti-inflammatory effect and therefore a possible role in the treatment of inflammatory diseases or in functional cosmetics.