• Molecules and Cells
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• v.27 no.2
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• pp.251-255
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• 2009

Sepsis is the leading cause of death in critically ill patients. Today, around 60% of all cases of sepsis are caused by Gram-negative bacteria. The cell wall component lipopolysaccharide (LPS) is the main initiator of the cascade of cellular reactions in Gram-negative infections. The core receptors for LPS are toll-like receptor 4 (TLR4), MD-2 and CD14. Attempts have been made to antagonize the toxic effect of endotoxin using monoclonal antibodies against CD14 and synthetic lipopolysaccharides but there is as yet no effective treatment for septic syndrome. Here, we describe an inhibitory effect of a phosphatidylethanolamine derivative, PE-DTPA (phosphatidylethanolamine diethylenetriaminepentaacetate) on LPS recognition. PE-DTPA bound strongly to CD14 ($K_d$, $9.52{\times}10^{-8}M$). It dose dependently inhibited LPS-mediated activation of human myeloid cells, mouse macrophage cells and human whole blood as measured by the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and nitric oxide, whereas other phospho-lipids including phosphatidylserine and phosphatidylethanolamine had little effect. PE-DTPA also inhibited transcription dependent on $NF-{\kappa}B$ activation when it was added together with LPS, and it rescued LPS-primed mice from septic death. These results suggest that PE-DTPA is a potent antagonist of LPS, and that it acts by competing for binding to CD14.

• Journal of Microbiology and Biotechnology
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• v.30 no.9
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• pp.1282-1289
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• 2020

Previously, we performed an in silico analysis of the Periplaneta americana transcriptome. Antimicrobial peptide candidates were selected using an in silico antimicrobial peptide prediction method. It was found that periplanetasin-5 had antimicrobial activity against yeast and gram-positive and gram-negative bacteria. In the present study, we demonstrated the anti-inflammatory activities of periplanetasin-5 in mouse macrophage Raw264.7 cells. No cytotoxicity was observed at 60 ㎍/ml periplanetasin-5, and treatment decreased nitric oxide production in Raw264.7 cells exposed to lipopolysaccharide (LPS). In addition, quantitative RT-PCR and enzyme-linked immunosorbent assay revealed that periplanetasin-5 reduced cytokine (tumor necrosis factor-α, interleukin-6) expression levels in the Raw264.7 cells. Periplanetasin-5 controlled inflammation by inhibiting phosphorylation of MAPKs, an inflammatory signaling element, and reducing the degradation of IκB. Through LAL assay, LPS toxicity was found to decrease in a periplanetasin-5 dose-dependent manner. Collectively, these data showed that periplanetasin-5 had anti-inflammatory activities, exemplified in LPS-exposed Raw264.7 cells. Thus, we have provided a potentially useful antibacterial peptide candidate with anti-inflammatory activities.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.1
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• pp.47-78
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• 1999

Hoichunyonggyuksan(HCYGS) and Yongseksan(YSS) are important prescriptions that have been used in oriental medicine for stomatitis and wound healing. The study was done to evaluate the inhibitory effects of cytotoxicity, formation of superoxide on the macrophage and neutrophil, prostaglandins($PGE_2$), interleukins($IL-1{\Beta}$), collagenase activity and synthesis of collagen and DNA. The results were obtained as fo1lows: 1. HCYGS and YSS were not showed the proliferation difference of human fibroblast and monocyte in all concentrations to be experimented and in result, it was concluded that they have no cytotoxicity. 2. YSS inhibited the formation of superoxide to $48\% at the concentration of $0.001\%$ in the mouse monocyte. 3. HCYGS inhibited the formation of superoxide to $13\%$ at the concentration of $0.001\%$ as compared with control in the human monocyte. 4. HCYGS and YSS inhibited the formation of superoxide to $25\%\;and\;35\%$ respectively at the concentration of $0.0001\%\;and\;HCYGS\;showed\;38\%$ inhihitory rate on the formation of superoxide at concentration of $0.001\%$ in the human neutrophil. 5. The concentration of inhibiting the production of prostaglandins($PGE_2$) to $11\%$ in the human monocyte stimulated with E. coli were $0.01\%$ of HCYGS. 6. The concentration of inhibiting the production of interleukins($IL-l{\Beta}$) to $43\%\;and\;39\%$ in the human monocyte stimulated with E. coli were $0.01\%$ of HCYGS and YSS. 7. HCYGS and YSS didn't influence on collagen synthesis and total protein in fibroblasts. 8. HCYGS and YSS inhibited the collagenase activity to $22\%\;and\;19\%\;at\;0.1\%,\;45\%\;and\;56\%\;at\;0.2\%,\;57\%\;and\;52\%$ at $0.5\%$ respectively, but YSS exerted the inhibitory effect on collagenase activity to $27\%$ at the lower concentration of $0.01\%$. 9. HCYGS and YSS didn't show the faster recovary than control group hut exerted the consistant effect on the anti-inflammations and the formation of granulation tissue.

• Korean Journal of Microbiology
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• v.54 no.1
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• pp.18-23
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• 2018

A new naturally occurring benzoic acid derivative, benzyl 2,4-di(benzyloxy)benzoate (1) and six known compounds (2-7) were isolated from the fungus, Preussia sp. found in frozen soil of the Himalaya Mountain. The structures of the new compound, together with the known compounds were determined by 1D-and 2D-NMR experiments, as well as comparison with published values. In addition, to the best of our knowledge, the known compounds 2-7 were isolated for the first time from the genus Preussia and the family Sporormiaceae. The isolates were evaluated for cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production induced by lipopolysaccharide (LPS) in mouse macrophage RAW 264.7 cells in vitro. Compounds 1 and 2 inhibited NO production by 50.7% and 88.5% at a concentration of 100 mg/ml, respectively.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1249-1253
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• 2006

The fractions of Capsosiphon fulvescens were studied to verify the anticancer and immunostimulating activity. The fractions from the ethanol extract of C. fulvescens were prepared by the systematic extraction procedure with the solvents such as hexane, ethyl ether, methanol, butanol and H$_2$O. The cytotoxic effects of C. fulvescens fractions against human leukemia cell line U937, mouse neuroblastoma cell line (NB41A3), human hepatoma cell line (HepG2)and rat glioma cell line (C6) were investigated. Ethyl ether fraction of C. fulvescens showed the highest cytotoxicity against all four cell lines tested. In addition, H$_2$O fraction also showed relatively high cytotoxicity. Dose dependent patterns were observed on all four cell lines. The immune-stimulating effects of C. fulvescens fractions on rat macrophage cell line (RAW 264.7) were also investigated. All five fractions of C. fulvescens extract stimulated NO production with concentration dependant manner. These results suggest that C. fulvescens may be a useful candidate for a natural antitumor and immune-stimulating agent.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.3
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• pp.155-165
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• 2012

Objective : The object of this study is to confirm the immune enhancement effect of Rubus coreanus Miquel (RC) (30% EtOH extract) on RAW264.7 mouse macrophage cell line. Methods : RAW264.7 cells were treated with $10-500{\mu}g/mL$ RC for 24 hours. Cell viability was then measured using WST assays. Levels of intracellular NO and ROS were measured by Griess reagent and DCFH-DA staining respectively. Levels of iNOS and COX-2 mRNA was determined by RT-PCR. Secretion levels of IL-$1{\beta}$ and IL-6 cytokines were evaluated by sandwich ELISA assay. Western blot analysis was performed to measure the levels of intracellular molecules related to MAPKs pathways. Results : RC suppressed the growth of RAW264.7 cells. RC increased the production of NO and ROS. RC increased the mRNA and protein levels of COX-2 and iNOS. RC augmented the levels of secreted IL-$1{\beta}$ and IL-6 cytokines. RC increased MAPKs phosphorylation. Conclusion : In summary, our result shows that RC has inflammatory effect increasing the levels of NO, ROS and secreted cytokines and activating MAPKs. Hence, RC seems to have an immune enhancement effect.

• Parasites, Hosts and Diseases
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• v.44 no.2 s.138
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• pp.101-116
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• 2006

Vaginal trichomoniasis, caused by Trichomonas vaginalis, is the most common sexually transmitted disease. More than 170 million people worldwide are annually infected by this protozoan. In the Republic of Korea, 10.4% of women complaining of vaginal symptoms and signs were found to be infected with T. vagina/is. However, despite its high prevalence, the pathogenesis of T. vaginalis infection has not been clearly characterized although neutrophil infiltration is considered to be primarily responsible for the cytologic changes associated with this infection. We hypothesized that trichomonads in the vagina sometime after an acute infection secrete proteins like excretory-secretory product that have a chemotactic effect on neutrophils, and that these neutrophils are further stimulated by T. vaginalis to produce chemokines like IL-8 and $GRO-\alpha$, which further promote neutrophil recruitment and chemotaxis. Thus, neutrophil accumulation is believed to maintain or aggravate inflammation. However, enhanced neutrophil apoptosis induced by live T. vaginalis could contribute to resolution of inflammation. Macrophages may constitute an important component of host defense against T. vaginalis infection. For example, mouse macrophages alone and those activated by lymphokines or nitric oxide are known to be involved in the extracellular killing of T. vaginalis. In the host, T. vaginalis uses a capping phenomenon to cleave host immunoglobulins with proteinases and thus escape from host immune responses. Recently, we developed a highly sensitive and specific diagnostic polymerase chain reaction (PCR) technique using primers based on a repetitive sequence cloned from T. vaginalis (TV-E650), and found that the method enables the detection of T. vaginalis at concentrations as low as 1 cell per PCR mixture.

• Molecules and Cells
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• v.23 no.3
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• pp.398-404
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• 2007

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in various pathophysiological processes such as inflammation and carcinogenesis. In a search for inhibitors of COX-2 and iNOS production we found that extracts of Stewartia koreana strongly inhibited NO and $PGE_2$ production in LPS-treated macrophage RAW 264.7 cells. We have now shown that the mRNA and protein levels of iNOS and COX-2 are reduced by the Stewartia koreana extract (SKE). SKE inhibited expression of an NF-${\kappa}B$ reporter gene in response to LPS, and gel mobility shift assays revealed that SKE reduced NF-${\kappa}B$ DNA-binding activity. The extract also inhibited LPS-induced phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Administration of the extract reduced the symptoms of arthritis in a collagen-induced arthritic mouse model. These results indicate that Stewartia extracts contain potentially useful agents for preventing and treating inflammatory diseases.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.9.1-9.10
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• 2018

Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.

• Korean Journal of Medicinal Crop Science
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• v.27 no.3
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• pp.208-217
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• 2019

Background: In the present study, we identified two cytotoxic compounds from the root of Rumex crispus L. using a bioassay-based method. Methods and Results: Compared with the other fractions, the diethyl ether ($Et_2O$) fraction of R. crispus root extract exhibited the strongest of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging effect [scavenging concentration 50% $(SC_{50})=63.8{\pm}1.47{\mu}g/m{\ell}$], nitric oxide (NO) production inhibitory effect on the mouse macrophage cell line RAW264.7 [inhibitory concentration 50% $(IC_{50})=60.9{\pm}7.52{\mu}g/m{\ell}$] and cytotoxicity effect on the human hepatoma cell line, HepG2 [lethal concentration 50% $(LC_{50})=115.4{\pm}1.86{\mu}g/m{\ell}$]. According to the bioassay-based method, two cytotoxic compounds were purified from the $Et_2O$ fraction by using column chromatography and preparative high performance liquid chromatography (prep-HPLC). These two compounds were identified as parietin and chrysophanol by using nuclear magnetic resonance (NMR) and liquid chromatography quadruple time of flight mass spectrometry (LC-QTOF-MS). In addition, both parietin and chrysophanol exhibited a cytotoxicity effect on HepG2 cells, their $LC_{50}$ values were $169.1{\pm}17.67{\mu}M$ and $111.5{\pm}6.62{\mu}M$, respectively. Conclusions: Parietin and chrysophanol isolated from the $Et_2O$ fraction of the R. crispus root extract showed cytotoxicity in HepG2 cell.