• Title/Summary/Keyword: Inducible nitric oxide

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Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

  • Youn, Cha Kyung;Park, Seon Joo;Li, Mei Hong;Lee, Min Young;Lee, Kun Yeong;Cha, Man Jin;Kim, Ok Hyeun;You, Ho Jin;Chang, In Youp;Yoon, Sang Pil;Jeon, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.4
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    • pp.315-320
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    • 2013
  • Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

Antiproliferative effect of Chungjogupae-tang treatment was associated with the inhibition of prostaglandin E2 release and Telomere active in human lung carcinoma cells (인체폐암세포에서의 prostaglandin E2 생성과 Telomere 활성에 미치는 청조구폐탕의 영향에 관한 연구)

  • Kim, Hoon;Park, Dong-Il
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.19 no.2
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    • pp.26-39
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    • 2006
  • Objective : The effect of water extract of Chungjogupae-tang (CJGPT) was investigated on the growth of human lung carcinoma A549 cells. Methods : MTT assay and fluorescent microscope performed to compare and examine the efficacy of CJGPT treatment on the cytostaticity of lung cancer cells in proportion to time and doses, and DAPI staining and Western blot analysis were used to examine their effect on apoptosis. In addition the quantitative RT-PCR was used to examine to lung cancer cells growth and Progtaglandin E2 and Telomerase activity were measured Results : Exposure of A549 cells to CJGPT resulted in the growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The antiuoliferative effect by CJGPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. CJGPT treatment resulted in an up-regulation of cyclin-dependent kinase inhibitor p21(WAF1/CIPl) in a p53-independent fashion. We found that CJGPT treatment decreased the levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthease (iNOS) expression without significant changes in the expression of COX-1, which was correlated with a decrease in protaglandin E2 (PGE2) synthesis. CJGPT treatment also inhibited the levels of human telomerase reverse transcriptase (hTERT) and telomerase-associated protein (TEP)-1 mRNA expression, however the activity of telomerase was slightly increased by CJGPT treatment. Conclusion : These findings suggested that CJGPT-induced inhibition of human lung carcinoma A549 cell growth was connected with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of CJGPT.

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Effect of Hot Water Extract from Scutellaria barbata on the Macrophages Activated by Lipopolysaccharide (반지련 (Scutellaria barbata D. Don) 추출물이 lipopolysaccharide에 의해 활성화된 대식세포에 미치는 영향)

  • Shen, Ting;Lee, Yong-Jin;Cho, Jae-Youl
    • Korean Journal of Medicinal Crop Science
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    • v.16 no.5
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    • pp.313-319
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    • 2008
  • Scutellaria barbata was examined to evaluate its modulatory effects on the functional activation of macrophages under lipopolysaccharide (LPS) treatment. To do this, hot water extract (Sb-HWE) was prepared from Scutellaria barbata and several inflammatory parameters such as nitric oxide (NO) production, phagocytosis, reactive oxygen species (ROS) determination and intracellular signaling pathway were selected to be tested. Sb-HWE strongly blocked NO production in LPS-activated RAW264.7 cells in a dose-dependent manner. However, it did not suppress inducible NO synthase (iNOS). In agreement, Sb-HWE did not diminish inflammatory signaling composed of NF-${\kappa}B$ and its upstream activation signaling enzymes such as Akt and $I{\kappa}B{\alpha}$. Sb-HWE protected RAW264.7 cells from LPS-induced cytotoxicity up to 80% at 400\;{\mu}g/ml$. Furthermore, this extract blocked phagocytic uptake of FITC-dextran, while sodium nitroprusside (SNP)-induced ROS generation in RAW264.7 cells was not decreased. Therefore, our data suggest that Sb-HWE may have differential immunoregulatory function depending on macrophage-mediated immune responses.

Improving Effects on Rats with Reflux Esophagitis Treated with Combined Extract of Young persimmon fruit and Citrus peel (떫은감 진피 복합추출물의 급성 역류성 식도염 개선 효과)

  • Kwon, OJun;Lee, AhReum;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.31 no.1
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    • pp.25-31
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    • 2016
  • Objectives : The present study was conducted to evaluate protective effects of Combined Extract of young persimmon fruit and citrus peel (PCM) in Reflux Esophagitis(RE) rats.Methods : Twenty-four Sprague-Dawley (SD) rats were divided four groups and each group had six rats ; Normal group, RE control group, RE group treated PCM 50 ,100 mg/kg body weight group. Reflux esophagitis was induced that tied the pylorus and fundus in SD rats stomach. PCM was administered at 50, 100 mg/kg body weight 2 hrs prior to induction of RE. After 6 hrs, the effects of PCM treated rats were compared with those of normal and control rats. We have performed an analysis such as pH of stomach secretion, oxidative stress biomarkers in serum, and western blot.Results : The increased esophageal mucosa damage by RE was markedly improved by PCM treatment in a dose-dependent manner. Also, the administration of PCM decreased the elevated serum reactive oxygen species (ROS) and peroxynitrite (ONOO-) in serum. The protein expressions of anti oxidant such as SOD, catalase, GPx exhibited down-regulation by PCM treatment in tissues. And, PCM effectively reduce inflammatory cytokines such as inflammation-related proteins cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in RE rats. In addition, NFκB and p-IκBɑ were decreased in PCM-adiministrated RE rats. But there was no difference on stomach secretion pH between reflux esophagitis rats and PCM administration rat group.Conclusions : In conclusion, administration of PCM (50, 100 mg/kg body weight) made esophagus have less inflammation and injury by decreased NFκB path way. These findings suggest that PCM could have Improving effects on reflux esophagitis.

Magnoliae Cortex and maize modulate Porphyromonas gingivalis-induced inflammatory reactions

  • Kim, Jae-Yoon;Kim, Kyoung-Hwa;Kwag, Eun-Hye;Seol, Yang Jo;Lee, Yong Moo;Ku, Young;Rhyu, In-Chul
    • Journal of Periodontal and Implant Science
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    • v.48 no.2
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    • pp.70-83
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    • 2018
  • Purpose: The aim of this study was to evaluate the capacity of single and combined applications of the bark of the stems and roots of Magnolia officinalis Rehd. et Wils. (Magnoliae Cortex) and Zea mays L. (maize) to modulate inflammation in RAW 264.7 cells stimulated with Porphyromonas gingivalis. Methods: RAW 264.7 cells were stimulated with P. gingivalis, and Magnoliae Cortex and/or maize was added. Cytotoxicity and the capacity to modulate inflammation were determined with a methylthiazol tetrazolium (MTT) assay, nitrite production, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results: Treatment with Magnoliae Cortex and/or maize inhibited nuclear transcription factor ${\kappa}B$ ($NF-{\kappa}B$) pathway activation and nuclear p44/42 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthase (iNOS) protein expression in P. gingivalis-stimulated RAW 264.7 cells. Moreover, the treatments suppressed cytokines (prostaglandin $E_2$ [$PGE_2$], interleukin $[IL]-1{\beta}$, and IL-6) and nitrite production. Conclusions: Both Magnoliae Cortex and maize exerted an anti-inflammatory effect on P. gingivalis-stimulated RAW 264.7 cells, and this effect was more pronounced when the extracts were combined. These findings show that these extracts may be beneficial for slowing the progression of periodontal disease.

Effect of Sulfur Enriched Young Radish Kimchi on the Induction of Apoptosis in AGS Human Gastric Adenocarcinoma Cells

  • Bak, Soon-Sun;Kong, Chang-Suk;Rhee, Sook-Hee;Rho, Chi-Woong;Kim, Nak-Ku;Choi, Keyng-Lag;Park, Kun-Young
    • Preventive Nutrition and Food Science
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    • v.12 no.2
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    • pp.79-83
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    • 2007
  • The effects of young radish (YR, yeolmu in Korean) on the induction of apoptosis were examined in AGS human gastric adenocarcinoma cells. The young radish kimchi (YRK) were made of YR cultivated in the soil without (Control YR kimchi: C-YRK) and with 1,818 g/m$^{3}$ sulfur (Sulfur YR kimchi: S-YRK), respectively. Methanol extracts from S-YRK exhibited higher inhibitory effect on the growth of AGS human gastric adenocarcinoma cells in a time dependent-manner compared to C-YRK at the same concentration. 4,6-diamidino-2-phenylindole (DAPI) staining showed that S-YRK induced apoptosis accompanied by the increased Bax but decreased Bcl-2 in mRNA expression. Moreover, S-YRK decreased the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA expressions. The results suggested that S-YRK cultivated in the presence of sulfur elicited stronger anticancer activity than C-YRK in vitro. Dietary intakes of S-YRK may be beneficial to decrease the risk of cancer.

Antioxidant and Anti-inflammation Effects of Water Extract from Buckwheat (메밀 추출물의 항산화 및 항염증 효능)

  • Kang, Hyun Woo
    • Culinary science and hospitality research
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    • v.20 no.6
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    • pp.190-199
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    • 2014
  • This study was conducted to investigate the effects of the hot water extract from buckwheat (WEB) in RAW-264.7 macrophage cells against lipopolysaccharide (LPS). In these experiments, we evaluated the anti-inflammatory effects of WEB by measuring MTT assay, nitric oxide (NO), inducible NOS (iNOS) production, and cyclooxygenase-2 (COX-2) expression by Western blotting. The extracts showed a protective effect by increasing cell viability on LPS in RAW264.7 cells. WEB (0.25, 0.5, and 1.0 mg/mL) significantly suppressed LPS-stimulated production of NO. Also, WEB reduced the expression of iNOS and COX-2 proteins. The present results show that WEB has potent anti-inflammatory effects on RAW264.7 cells. In addition, WEB has various antioxidant effects as a result of 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) which possess a radical scavenging activity. The total polyphenol and flavonoid contents of the WEB were $13.22{\pm}3.69mg\;GAE/g$ extract and $38.53{\pm}5.20mg\;CE/g$ extract respectively. The present results give the understanding of biological activities of buckwheat and encourage their application for supplements.

Anti-oxidant and Anti-inflammatory Effects of Chulbu-tang (출부탕(朮附湯) 추출물의 항산화 및 항염증에 대한 효과)

  • Hyeong, Kyun;Won, Je-Hoon;Woo, Chang-Hoon
    • Journal of Korean Medicine Rehabilitation
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    • v.30 no.3
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    • pp.71-87
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    • 2020
  • Objectives Even though the various alternative herbal medicine has applied for osteoarthritis (OA) treatment, its scientific proof remains uncertain. The aim of the present study evaluates the effects of Chulbu-tang on inflammatory responses in a monosodium iodoacetate (MIA)-induced osteoarthritis rat model. Methods OA rat model was established by MIA injection in intra-joint of rats. 7 days after, OA rats except OA control rats were administrated Chulbu-tang (100 or 200 mg/kg) or Indomathacin (5 mg/kg) once a day for 14 days. The weight-bearing ability of hind paws were measured when group isolation 0, 7, and 14 days. Western blotting was performed to examine the knockdown/overexpressing efficiency of Chulbu-tang. In addition, cartilage destruction was measured histologically. Results Chulbu-tang treatment significantly reduced the protein expressions of inflammatory mediators such as inducible nitric oxide synthase and cyclooxygenase 2, and inhibited inflammatory cytokines including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6 through nuclear factor-kappa B (NF-κB) inactivation. Moreover, anti-oxidant enzymes such as superoxide dismutase and glutathione peroxidase-1/2 through nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway significantly increased. Our findings indicate that Chulbu-tang has the potential therapeutic effect on OA through inhibiting the inflammatory responses via inactivating NF-κB signaling pathway. In addition, upregulation of Nrf2 led to anti-oxidant effects. Conclusions Taken together, Chulbu-tang is believed to have antioxidant, anti-inflammatory effects, and cartilage protection for arthritis-causing rats.

Antioxidant and Anti-inflammatory Effects of Yam (Dioscorea batatas Decne.) on Azoxymethane-induced Colonic Aberrant Crypt Foci in F344 Rats

  • Son, In Suk;Lee, Jeong Soon;Lee, Ju Yeon;Kwon, Chong Suk
    • Preventive Nutrition and Food Science
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    • v.19 no.2
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    • pp.82-88
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    • 2014
  • Yam (Dioscorea batatas Decne.) has long been used as a health food and oriental folk medicine because of its nutritional fortification, tonic, anti-diarrheal, anti-inflammatory, antitussive, and expectorant effects. Reactive oxygen species (ROS), which are known to be implicated in a range of diseases, may be important progenitors of carcinogenesis. The aim of this study was to investigate the modulatory effect of yam on antioxidant status and inflammatory conditions during azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. We measured the formation of aberrant crypt foci (ACF), hemolysate antioxidant enzyme activities, colonic mucosal antioxidant enzyme gene expression, and colonic mucosal inflammatory mediator gene expression. The feeding of yam prior to carcinogenesis significantly inhibited AOM-induced colonic ACF formation. In yam-administered rats, erythrocyte levels of glutathione, glutathione peroxidase (GPx), and catalase were increased and colonic mucosal gene expression of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, and GPx were up-regulated compared to the AOM group. Colonic mucosal gene expression of inflammatory mediators (i.e., nuclear factor kappaB, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, and interleukin-1beta) was suppressed by the yam-supplemented diet. These results suggest that yam could be very useful for the prevention of colon cancer, as they enhance the antioxidant defense system and modulate inflammatory mediators.

The Ameliorative Effects of Korean Bean-Leaves on Inflammation and Liver Injury in Obese Rat Model

  • Jin, Byung-Moon;Choi, Seok-Cheol;Lee, Hye-Sook;Jung, Sang-Bong;Hyun, Kyung-Yae
    • Biomedical Science Letters
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    • v.19 no.3
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    • pp.195-205
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    • 2013
  • Obesity may cause metabolic syndrome and adult diseases. This study was undertaken to investigate the ameliorative or useful effects of beanleaves on inflammation and liver damage in obese rat models. Rats were divided into three groups: a control group (normal diet, n=6), a fat diet group (45%-fat diet, n=7), and a bean leaf group (45%-fat+Korean bean leaves diet, n=7). Body weights in the bean leaf group were lower than those of the fat group (P<0.05). Serum tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and prostaglandin $E_2$ ($PGE_2$) concentrations were lower in both the control and bean leaf groups than in the fat group (P<0.001). TNF-${\alpha}$ concentrations in the bean leaf group were slightly higher than in the control group but statistically significant (P<0.05). The bean leaf group histologically exhibited lower fatty degeneration, spotty necrosis, and leukocyte infiltrations in hepatic tissues than those of the fat group. In the homogenized liver tissues, the cyclooxygenase-2 (COX-2) gene was only expressed in the fat group. The gene expression levels of hepatic TNF-${\alpha}$, inducible nitric-oxide synthase, peroxiome proliferator-activated receptor-${\alpha}$ (PPAR-${\alpha}$), poly (ADP-ribose) polymerase (PARP), and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) were weaker in the bean leaf group than in the fat group. These results suggest that adding bean-leaves to the diet may ameliorate obesity-induced systemic inflammation and liver damage and that bean leaves may be a useful food for preventing obesity and thereby metabolic syndrome and adult diseases.