• YAKHAK HOEJI
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• v.60 no.3
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• pp.128-134
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• 2016

L1 cell adhesion molecule (L1CAM) is a cell surface molecule to initiate a variety of cellular responses through interacting with other cell adhesion molecules in a homophilic or heterophilic manner. Although its expression was found to be upregulated in some tumor cells, including cholangiocarcinomas, and ovarian cancers, and many studies have investigated the role of L1CAM in these cancers, its role in inflammatory responses has been poorly understood. In this study, we explored the role of L1CAM in macrophage-mediated inflammatory responses. L1CAM significantly suppressed the production of nitric oxide (NO), but induced cell proliferation in RAW264.7 cells. L1CAM expression was detectable, but its expression was markedly decreased by lipopolysaccharide (LPS) in RAW264.7 cells. In addition, the expression of pro-inflammatory genes, such as tumor necrosis factor (TNF)-${\alpha}$, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) induced by LPS was dramatically suppressed by L1CAM in RAW264.7 cells. L1CAM inhibited the transcriptional activities of NF-${\kappa}B$ and AP-1 while its cytoplasmic domain deletion form, $L1{\Delta}CD$ did not suppressed their activities in RAW264.7 cells. Moreover, L1CAM suppressed nuclear translocation of p65 and p50 as well as c-Jun, c-Fos and p-ATF2 which are transcription factors of NF-${\kappa}B$ and AP-1, respectively. In conclusion, L1CAM suppressed inflammatory responses in macrophages through inhibiting NF-${\kappa}B$ and AP-1 pathways.

• Korean Journal of Pharmacognosy
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• v.44 no.3
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• pp.291-297
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• 2013

Sophorae Flos (SF), a composite of flowers and flower-buds of Sophora japonica, has long been used in traditional Korean and Chinese medicines for the treatment of hemostasis and inflammation. In this study, we investigated anti-inflammatory effect of four EtOH extracts at the difference in blooming stages of flowers on LPS-induced inflammation in RAW264.7 cells. We classified the flowers of Sophora japonica with SF-1 (length of flower is shorter than calyx), SF-2 (length of calyx is shorter than flower), SF-3 (full bloom), and SF-4 (not blooming at all). We examined HPLC analysis, whether quercetin and rutin are major component of these Sophorae Flos extracts or not. As a result, SF-1 contained quercetin, but the others did not. In addition, quercetin, SF-1, and SF-4 act on the suppression of pro-inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, nitric oxide (NO), prostaglandin E2 ($PGE_2$) against lipopolysaccharide (LPS)-induced activation in RAW264.7 cells. Of these, SF-1 showed the best anti-inflammatory effect. These results suggest that Sophorae Flos with the highest content of quercetin would be used for the treatment of various inflammation diseases.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.3
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• pp.201-208
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• 2022

Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.103-103
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• 2022

Ganghwaljetongyeum (GHJTY) is a complex herbal decoction comprising 18 plants; it is used to treat arthritis. In order to develop a new anti-arthritic herbal medication, we selected 5 out of 18 GHJTY plants by using bioinformatics analysis. The new medication, called ChondroT, comprised water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex. This study was designed to investigate its chondroprotective and anti-inflammatory effects to develop an anti-arthritic herb medicine. ChondroT was validated using a convenient and accurate high-performance liquid chromatography. photodiode array (HPLC-PDA) detection method for simultaneous determination of its seven reference components. The concentrations of the seven marker constituents were in the range of 0.81-5.46 mg/g. The chondroprotective effects were evaluated based on SW1353 chondrocytes and matrix metalloproteinase 1 (MMP1) expression. In addition, the anti-inflammatory effects of ChondroT were studied by Western blotting of pro-inflammatory enzymes and by enzyme-linked immunosorbent assay (ELISA) of inflammatory mediators in lipopolysaccharides (LPS)-induced RAW264.7 cells. ChondroT enhanced the growth of SW1353 chondrocytes and also significantly inhibited IL-1β-induced MMP-1 expression. However, ChondroT did not show any effects on the growth of HeLa and RAW264.7 cells. The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was induced by LPS in RAW264.7 cells, which was significantly decreased by pre-treatment with ChondroT. In addition, ChondroT reduced the activation of NF-κB and production of inflammatory mediators, such as IL-1β, IL-6, PGE2, and nitric oxide (NO) in LPS-induced RAW264.7 cells. These results show that ChondroT exerted a chondroprotective effect and demonstrated multi-target mechanisms related to inflammation and arthritis. In addition, the suppressive effect was greater than that exhibited by GHJTY, suggesting that ChondroT, a new complex herbal medication, has therapeutic potential for the treatment of arthritis.

• Journal of Acupuncture Research
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• v.40 no.4
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• pp.368-376
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• 2023

Background: Although bee venom (BV) has clinical benefits in osteoarthritis and rheumatoid arthritis, it has not been tested as treatment for gouty arthritis. Moreover, in vitro, BV has been proven to exhibit anti-inflammatory and positive effects on osteoarthritis, but only limited evidence can confirm its beneficial effects on gout. Thus, this study aims to assess the anti-inflammatory effects of BV on monosodium urate (MSU)-induced THP-1 monocytes. Methods: THP-1 monocytes were differentiated into mature macrophages using phorbol 12-myristate 13-acetate (PMA) and pretreated for 6 hours with BV and a Caspase-1 inhibitor in a physiologically achievable range of concentrations (BV, 0.1-1 ㎍/mL; Caspase-1 inhibitor, 1-10 μM), followed by MSU crystal stimulation for 24 hours. The secretions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, IL-8, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) were increased in the MSU crystal-stimulated THP-1 cells. Results: Caspase-1 inhibitors suppressed the production of all mediators in a dose-dependent manner. BV worked on equal terms with Caspase-1 inhibitors and showed more satisfactory effects on TNF-α, PGE2, COX-2, and inducible nitric oxide synthase (iNOS). Moreover, the western blot analysis revealed that BV regulated the transcriptional levels of these mediators via the suppression of extracellular signal-regulated kinase (ERK) pathway activation. Conclusion: The results of the present study clearly suggest that BV inhibits MSU-induced inflammation in vitro, suggesting a possible role for BV in gout treatment.

• The Korean Journal of Food And Nutrition
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• v.37 no.2
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• pp.110-122
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• 2024

This study investigated major constituents and anti-inflammatory effects of an ethanol extract of Platycodon grandiflorum leaves. Through HPLC analysis, chlorogenic acid and luteolin-7-O-glucoside were identified as predominant constituents in the ethanol extract. Their anti-inflammatory effects were evaluated using murine macrophage (RAW 264.7 cells) and human lung carcinoma cells (NCI-H292 & A549). The ethanol extract significantly (p<0.01) inhibited the production of nitrite, interleukin-6 (IL-6), and prostaglandin E2 (PGE2) induced by lipopolysaccharide (LPS) in RAW 264.7 cells. Furthermore, the ethanol extract suppressed the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) proteins in RAW 264.7 cells stimulated with LPS. In NCI-H292 and A549 cells, treatment with the ethanol extract significantly (p<0.05) decreased levels of pro-inflammatory cytokines IL-6 and IL-8 induced by IL-1β. The phosphorylation of ERK rather than JNK in the mitogen-activated protein kinase signaling pathway was observed to be a more important mediator in the down-regulation of pro-inflammatory cytokines in NCI-H292 cells. These findings suggest that the ethanol extract of Platycodon grandiflorum leaves containing luteolin-7-O-glucoside exhibits promising anti-inflammatory properties.

• Journal of Life Science
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• v.27 no.2
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• pp.187-193
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• 2017

As a part of ongoing research to elucidate and characterize antiinflammatory nutraceuticals, the crude extracts from Atriplex gmelinii C. A. Mey. and their solvent-partitioned fractions were tested for their antiinflammatory potential in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophages. The crude extracts of A. gmelinii C. A. Mey. were fractioned according to polarity with n-hexane, 85% aqueous methanol (85% aq. MeOH), n-butanol, and $H_2O$. Their antiinflammatory activities were investigated in LPS-induced inflammation in mouse macrophages by measuring nitric oxide (NO) generation and mRNA expression of inflammation mediators, namely, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-$1{\beta}$ ($IL-1{\beta}$), and IL-6. As a result, we confirmed that the crude extracts of A. gmelinii C. A. Mey. inhibited LPS-stimulated NO production and mRNA expression of iNOS and COX-2 as important inflammatory factors. The inhibition of NO production through the downregulation of important inflammatory factors such as iNOS, COX-2, $IL-1{\beta}$, and IL-6 was found by treatment with all solvent-partitioned fractions. Among all tested fractions, 85% aq. MeOH showed the strongest antiinflammatory response. Based on the current results, A. gmelinii C. A. Mey. was suggested to possess natural antiinflammatory components, indicating that it could be used as a valuable source of antiinflammatory substances.

• Journal of Life Science
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• v.28 no.2
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• pp.216-222
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• 2018

Desmodium heterocarpon is one of vines belongs to Fabaceae family, mainly distributed in Asian countries such as Korea and Japan. This study was conducted to explore new nutraceutical resources from the plant kingdom possessing biological activities. To fulfill this purpose, the anti-oxidative and anti-inflammatory activities of D. heterocarpon ethanol extract (DHEE) were evaluated by 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity assay, reactive oxygen species (ROS) scavenging activity assay, nitric oxide (NO) inhibitory activity assay, and the analysis of related protein expressions by Western blot hybridization. DHEE exhibited potent anti-oxidative activity as confirmed by DPPH radical scavenging capacity against DPPH similar with ascorbic acid, a well-known anti-oxidative agent, used as a positive control. DHEE also effectively suppressed hydrogen peroxide ($H_2O_2$)-induced ROS on RAW 264.7 murine macrophage cells. Furthermore, DHEE induced the expression of the anti-oxidative enzyme heme oxygenase 1 (HO-1), and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2) as a dose dependent manner. DHEE inhibited lipopolysaccharide (LPS) induced nitric oxide (NO) formation as a consequence of inducible NO synthase (iNOS) down regulation. Taken together, these results suggest that DHEE has anti-oxidative and anti-inflammatory activities and thus appears to be useful sources as potential anti-oxidant and anti-inflammatory agents. The identification of active compounds that confer biological activities of DHEE might be needed.

• The Korean Journal of Food And Nutrition
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• v.29 no.3
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• pp.431-437
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• 2016

Macrophages play a pivotal role in the innate and adaptive immune systems. This study investigated the immuno-modulatory activities of polysaccharides separated from Chrysanthemum zawadskii var. latilobum (CZPS) in macrophages. Polysaccharides from Chrysanthemum zawadskii var. latilobum were extracted by the ethanol precipitation method. RAW 264.7 mouse macrophage cell line was treated with CZPS (4 to $128{\mu}g/mL$), and there was no cytotoxicity at a dose below $32{\mu}g/mL$. The levels of nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, IL-$1{\beta}$) production in the CZPS treated group ($32{\mu}g/mL$) were $6.5{\pm}0.12{\mu}m$ (NO), $1252.8{\pm}79.85$ (TNF-${\alpha}$), $305.4{\pm}29.41$ (IL-6), and $683.3{\pm}59.71$ (IL-$1{\beta}$), respectively, and they were significantly increased when compared to the control group; $2.2{\pm}0.03{\mu}m$ (NO), $452.3{\pm}38.34$ (TNF-${\alpha}$), $31.7{\pm}5.75$ (IL-6), and $184.1{\pm}11.52$ (IL-$1{\beta}$). Additionally, protein expression of inducible nitric oxide synthase (iNOS) and phosphorylation of MAPKs and NF-${\kappa}B$ expression were significantly increased upon CZPS treatment. Therefore, these results indicated that polysaccharides separated from Chrysanthemum zawadskii var. latilobum (CZPS) may have a potential immunomodulatory activity in macrophages through MAPKs and NF-${\kappa}B$ signaling, and this information is useful for the development of immune enhancing adjuvant materials using a natural ingredient.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.3
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• pp.297-305
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• 2014

Red ginseng (RG) contains specific ginsenosides (Rg2, Rg3) which show various pharmacological effects and absorption rate in the body better than panax ginseng. Therefore many people have been used it for health for a long time. Furthermore, many researchers have been studying its biological activities for a long times because fermentation generates lots of beneficial small molecules good for health. In this study, we fermented red ginseng with mycelium of Leatiporus sulphures var. miniatus for 7 days. As a result, we found that three ginsenosides Rg1, Re and Rb2 were decreased from 0.24, 0.25, 0.16 mg/g to 0.12, 0.1, 0.03 mg/g respectively HPLC analysis. In addition, we studied biological activities of fermented red ginseng (FRG) about skin ageing such as anti-inflammation, cell migration, anti-oxidation, collagen type 1 synthesis, and MMP-1 inhibition activities. As a result, FRG were shown higher anti-inflammatory and cell migration promoting activities than RG. FRG inhibited production of nitric oxide (NO) and mRNA expression of inducible nitric oxide synthase (iNOS) and decreased interleukin (IL)-6 induced by LPS stimulation in RAW 264.7 cells. In conclusion, this study suggest that FRG could be a potential source as a new natural anti-inflammatory agent.