• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.594-602
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• 2009

Purpose : Transforming growth factor (TGF)-${\beta}1$ reportedly increases neuronal survival by inhibiting the induction of inducible nitric oxide synthase (NOS) in astrocytes and protecting neurons after excitotoxic injury. However, the neuroprotective mechanism of $TGF-{\beta}1$ on hypoxic-ischemic (HI) brain injury in neonatal rats is not clear. The aim of this study was to determine whether $TGF-{\beta}1$ has neuroprotective effects via a NO-mediated mechanism and N-methyl-D-aspartate (NMDA) receptor modulation on perinatal HI brain injury. Methods : Cortical cells were cultured using 19-day-pregnant Sprague-Dawley (SD) rats treated with $TGF-{\beta}1$ (1, 5, or 10 ng/mL) and incubated in a 1% O2 incubator for hypoxia. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 h of hypoxic exposure (7.5% $O_2$). $TGF-{\beta}1$ (0.5 ng/kg) was administered intracerebrally to the rats 30 min before HI brain injury. The expressions of NOS and NMDA receptors were measured. Results : In the in vitro model, the expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS) increased in the hypoxic group and decreased in the 1 ng/mL $TGF-{\beta}1-treated$ group. In the in vivo model, the expression of inducible NOS (iNOS) decreased in the hypoxia group and increased in the $TGF-{\beta}1$-treated group. The expressions of eNOS and nNOS were reversed compared with the expression of iNOS. The expressions of all NMDA receptor subunits decreased in hypoxia group and increased in the $TGF-{\beta}1$-treated group except NR2C. Conclusion : The administration of $TGF-{\beta}1$ could significantly protect against perinatal HI brain injury via some parts of the NO-mediated or excitotoxic mechanism.

• Journal of Life Science
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• v.34 no.4
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• pp.245-253
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• 2024

We investigated to analyze total flavonoid content and fatty acid composition of Stachys sieboldii Miq root. In order to determine antioxidant and anti-inflammatory effects of fractions from S. sieboldii Miq. root, we conducted 1.1-Diphenyl-2-picryhydrazyl (DPPH) and 2,2'-Azino-bis (3-ethylbenothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS) assays for antioxidant and measured nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 cells. In addition, we examined an inhibitory effect of fractions from S. sieboldii Miq. root on smad signaling induced by transforming growth factor (TGF) β. Among the fractions, n-butanol (n-BuOH) fraction showed the highest flavonoid content (16.67 mg/g), followed by n-Hexane, water and 85% aqueous methanol (85% aq. MeOH) fractions. The fatty acid composition of S. sieboldii Miq. root was in the following order : n-6 fatty acids (54.3%) > n-3 fatty acids (21.2%) > saturated fatty acids (19.7%) > n-9 fatty acids (3.6%). As a result of the antioxidant efficacy, the DPPH and ABTS assays showed that n-BuOH fraction had higher scavenging activity compared to other fractions. Inhibitory effect on NO production showed that all fractions decreased LPS-induced NO production, indicating an anti-inflammatory activity of S. sieboldii Miq. root. 85% aq. MeOH and water fractions showed a higher efficacy in inhibiting transforming growth factor (TGF) β induced smad signaling. From the results, it suggests that food processing products using S. sieboldii Miq. root will be developed as a functional food for promoting health.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.120-128
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• 2005

Background : Insulin-like growth factor binding protein (IGFBP)-3 regulates non-small cell lung cancer(NSCLC) cell proliferation in vitro and in vivo by inhibiting IGF-mediated signaling pathways. To have better strategies for the treatment of lung cancer, we analyzed the combining effects of adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and SCH66336, a farnesyl transferase inhibitor (FTI) designed to block Ras-mediated proliferative signaling pathways. Methods : To measure the combining effects of Ad5CMV-BP3 and SCH66336 on the proliferation of NSCLC cells, human NSCLC cell lines (H1299, H596, A549, H460, and H358), SCH66336, recombinant adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and athymic nude mice were used in these experiments. Results : The combination of Ad5CMV-BP3 and SCH66336 produced a synergistic enhancement in antiproliferative effects over a range of clinically achievable concentrations in a variety of NSCLC cell lines. Furthermore, we observed a significant reduction in growth of NSCLC xenograft induced in athymic nude mice. Conclusion : In conclusion, this study demonstrated for the first time that the FTI SCH66336 synergizes with IGFBP-3 and enhances its apoptotic activity in NSCLC cells in vitro and in vivo. The combined treatment of Ad5CMV-BP3 and SCH66336 raises the possibility of using this regimen in clinic for the treatment of NSCLC.

• Microbiology and Biotechnology Letters
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• v.45 no.2
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• pp.101-109
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• 2017

This study investigated the effect of the dichloromethane fraction form Katsuwonus pelamis heart on anti-inflammatory responses in lipopolysaccharide-stimulated RAW 264.7 cells and mouse models. Ethanol extract was partitioned with dichloromethane, ethyl acetate, butanol, and water. Among the fractions, the dichloromethane fraction showed a significant decrease in nitric oxide (NO) and pro-inflammatory cytokines [interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$] production compared to ethanol extract. The dichloromethane fraction attenuated the expression of inducible nitric oxide synthase and nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65 proteins in a dose-dependent manner. In addition, the expression of phosphorylation of mitogen-activated protein kinases (MAPKs) was also inhibited by the dichloromethane fraction. Moreover, the administration of 10, 50, and 250 mg/kg body weight-dose dependently inhibited the formation of edema by croton-oil and the application of dichloromethane (2 mg/ear) significantly reduced epidermal and dermal thickness and the infiltrated mast cell numbers. Therefore, the dichloromethane fraction exhibited an anti-inflammation effect by inhibiting $NF-{\kappa}B$ and MAPK signaling activation in macrophages.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.929-937
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• 2016

The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

• Journal of Life Science
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• v.22 no.1
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• pp.41-48
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• 2012

Bee venom (BV) has been used in medicine to treat a variety of diseases including arthritis, rheumatism, and various cancers. Recent reports indicate that BV has anti-angiogenic effects, but the precise molecular mechanism underlying the effects of BV against colorectal cancer remains to be elucidated. We examined the effects of BV and its major components (melittin and apamin) on tumor angiogenesis and found that BV significantly decreased protein levels of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), an important factor involved in angiogenesis and tumor progression, in human colorectal carcinoma HCT116 cells. BV also suppressed the transcription of HIF-$1{\alpha}$ under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major target gene of HIF-$1{\alpha}$. We also found that these effects were mainly elicited by apamin, but not melittin. BV specifically inhibited the phosphorylation of ERK1/2 without changing the total levels of this protein, but had no effect on kinases of p38/JNK and AKT. Our results suggest that BV may inhibit human colorectal cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$ and VEGF expression, thereby providing a novel potential mechanism for the anticancer action of BV.

• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.347-355
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• 2008

Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.1
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• pp.75-94
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• 2008

Objectives : This study was to investigate the effects of GCP treatment on the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Arthritis was induced by injection of Monosodium lodoacetate(0.5mg) into knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of GCP by oraly for same duration. Normal group(n=8) was injected with normal saline and was taken distilled water for 20 days. Body weight was measured at 0, 5, 10, 15, 20 days after injection. Macroscopic examination and histopathological study on articular cartilage of knee joint were operated at 20 days after injection. Proteoglycan(PG) content of articular cartilages of knee joint was represented by safranine O staining, was measured at 20 days injection. Tumor necrosis $factor-{\alpha}$, $Interleukin-1{\beta}$, Interleukin-6 in synovial fluid were measured with ELISA kit at 20 days after injection. Immunohistochemical staining of COX-2, iNOS in knee joints were observed at 20 days after injection. Results : 1. Body weight of the treated group increased compare with control group at 20 days after injection. 2. Macroscopically, degree of osteoarthritis in the treated group were evaluated compared with the control group. 3. PG content in articular cartilage of the treated group was significantly increased compared with the control group. 4. Histopathologically, osteoarthritic scores of the treated group was significantly decreased compared with the control group. 5. $TNF-{\alpha}$ content in synovial fluid of the treated group was decreased compared with the control group. 6. $IL-1{\beta}$ content in synovial fluid of the treated group was significantly decreased compared with the control group. 7. Positive reaction of COX-2 in chondrocytes and synovial membrane of the treated group was faint compared with the control group. Conclusions : On the basis of these results, we concluded that GCP has inhibiting effects on the $IL-1{\beta}$ and COX-2 secretion of chondrocytes and synovial membrane in Monosodium lodoacetate-Induced osteoarthritis model of rats.

• Journal of the Korea Organic Resources Recycling Association
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• v.25 no.3
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• pp.99-111
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• 2017

The purpose of this study is to provide a design and operation technical guideline for meeting the appropriate design criteria to bio-gasification facilities treating organic wastes. Based on the results obtained during the field surveys, the overall design and operation guidelines for bio-gasification facilities, monitoring items, cycle and commissioning period were presented. According to the flow of anaerobic digestion process, Various design factors for bio-gasification facilities were proposed in this study. When designing the initial anaerobic digestion capacity, 10 ~ 30% of the treatment capacity was applied considering the discharge characteristics by the incoming organic wastes. At the import storage hopper process, limit concentration of transporting organic wastes was limited to TS 10 % or less, and limit concentration of inhibiting factor was suggested in operation of anaerobic digester. In addition, organic loading rate (OLR) was shown as $1.5{\sim}4.0kgVS_{in}/(m^3{\cdot}day)$ for the combined bio-gasification facilities of animal manure and food wastes. Desulfurization and dehumidification methods of biogas from anaerobic digestor and proper periods of liquifization tank were suggested in design guideline. It is recommended that the operating parameters of the biogasification facilities to be maintained at pH (acid fermentation tank 4.5~6.5, methane fermentation tank 6.0~8.0), temperature variation range within $2^{\circ}C$, management of volatile fatty acid and ammonia concentration less than 3,000 mg/L, respectively.

• Korean Journal of Food Science and Technology
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• v.47 no.1
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• pp.119-125
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• 2015

The aim of this study was to investigate the synergistic anti-inflammatory effect of rosmarinic acid (RA) and luteolin from perilla (Perilla frutescens L.) leaves in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. A combination of RA and luteolin more strongly inhibited the production of nitric oxide (NO), inducible NOS (iNOS), prostaglandin $E_2$ ($PGE_2$), and COX-2 than higher concentrations of RA or luteolin alone in LPS-stimulated RAW264.7 macrophages. The combined RA and luteolin synergistically inhibited the production of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and interleukin-$1{\beta}$ (IL-$1{\beta}$), in LPS-stimulated RAW264.7 macrophages. Furthermore, combined RA and luteolin more strongly suppressed NF-${\kappa}B$ activation than RA or luteolin alone, by inhibiting the degradation of inhibitor of NF-${\kappa}B(I{\kappa}B)$-${\alpha}$ and nuclear translocation of the p65 subunit of NF-${\kappa}B$ in LPS-stimulated RAW264.7 macrophages. Collectively, these results suggest that RA and luteolin in combination exhibit synergistic effects in suppression of LPS-induced inflammation in RAW264.7 macrophages.