• Title/Summary/Keyword: iNOS inhibitor

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Antiproliferative Effect of RST Associated with the Inhibition of Cyclooxygenase-2 Expression and Prostaglandin E2 Release in Human Lung Carcinoma Cells (산두근 추출물이 인체폐암세포의 COX-2 발현 및 PGE2 생성에 미치는 영향)

  • Kim, Kang-Tae;Eom, Hyun-Sup;Chi, Gyoo-Yong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.4
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    • pp.907-915
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    • 2007
  • In this study the effect of water extract of Sophora tonkinensis Gapnep (RST) was investigated on the growth of human lung carcinoma A549 cells. Exposure of A549 cells to RST resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay. The antiproliferative effect by RST treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. RST treatment did not induce the cell cycle arrest and the levels of tumor suppressor p53 as well as cyclin-dependent kinase inhibitor p21(WAF1/CIP1). It was found that RST treatment decreased the levels of cyclooxygenase (COX) -2 mRNA and protein expression without significant changes in the expression of COX-1 and inducible nitric oxide synthase (iNOS), which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. RST treatment also slightly inhibited the levels of human telomerase reverse transcriptase (hTERT) mRNA and protein expression, and the activity of telomerase. Taken together, these findings suggested that RST-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the inhibition of COX-2 expression and PGE2 production. These results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of RST.

Antiproliferative Effect and Apoptotic Mechanism of Extract of Corydalis Yanhusuo on Human Hepatocarcinoma Cells (현호색(玄胡索)이 인체간암세포 증식억제 및 apoptosis 유발에 미치는 영향)

  • Oh, Myun- Taek;Eom, Hyun-Sup;Chi, Gyoo-Yong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.6
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    • pp.1437-1449
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    • 2007
  • In this study, the effect of extract of Corydalis yanhusuo (ECT) used in Oriental medicine therapy was investigated on the cell growth and apoptosis of HepG2 human hepatoma cells. It was found that ECT could inhibit the cell growth effectively in a dose-dependent manner, which was associated with morphological change and apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. And we observed the effects of ECT on loss of mitochondrial membrane potential (MMP), using the JC-1 probe by DNA flow cytometric analysis. Apoptosis of HepG2 cells by ECT was associated with a down-regulation of anti apoptotic Bcl-2 expression, inhibitor of apoptosis proteins (IAPs) expression and proteolytic activation of caspase-3 and caspase-9. However, ECT did not affect the pro-apoptotic Bax expression and activity of caspase-8. ECT treatment also concomitant degradation and /or inhibition of poly (ADP-ribose) polymerase (PARP), phospholipase C-1 ($PLC{\gamma}1$). Furthermore, ECT treatment caused a dose-dependent inhibition of iNOS and cyclooxygenase-2 (Cox-2). Additionally ECT have been implicated in the regulation of telomerase expression. ECT treatment induced the down-regulation of telomerase reverse transcriptase mRNA (hTERT) expression of HepG2 cells. Taken together, these findings suggest that ECT may be a potential chemotherapeutic agent for the control of HepG2 human hepatoma cells.

Antiproliferative Effect of Chungjogupae-tang Treatment was Associated with the Inhibition of Prostaglandin E2 Release in Human Lung Carcinoma Cells (인체폐암세포의 증식 및 prostaglandin E2 생성에 미치는 청조구폐탕의 영향에 관한 연구)

  • Im, Jae-Hyung;Kim, Hoon;Byun, Mi-Kyeon;Kam, Chul-Woo;Park, Dong-Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.966-972
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    • 2006
  • 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 peformed 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 Prostaglandin E2 activity were measured. Results: Exposure of A549 cells to CJGPT respited in the growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The antiproliferative 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 (WAFl/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 prostaglandin E2 (PGE2) synthesis. 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.

Anti-Inflammatory Effects of Grasshopper Ketone from Sargassum fulvellum Ethanol Extract on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells

  • Kim, Min-Ji;Jeong, So-Mi;Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Ahn, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.29 no.5
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    • pp.820-826
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    • 2019
  • This study evaluated the anti-inflammatory potential of a grasshopper ketone (GK) isolated from the brown alga Sargassum fulvellum on lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophage cell line. GK was isolated and purified from the n-hexane fraction and its structure was verified on the basis of NMR spectroscopic data. GK up to $100{\mu}g/ml$ is not cytotoxic to RAW 264.7, and is an effective inhibitor of LPS-induced NO production in RAW 264.7 cells. The production of pro-inflammatory cytokines, including IL-6, $IL-1{\beta}$, and $TNF-{\alpha}$ was found significantly reduced in $0.1-100{\mu}g/ml$ dose ranges of GK treatment (p < 0.05). We confirmed the dose-dependent and significant inhibition of iNOS and COX-2 proteins expression. In addition, it has been shown that GK induces anti-inflammatory effects by inhibiting MAPKs (ERK, JNK, and p38) and $NF-{\kappa}B$ p65 phosphorylation. Our results show that the anti-inflammatory properties of GK may be due to the inhibition of the $NF-{\kappa}B$ and MAPKs pathways, which are associated with the attenuation of cytokine secretion.

Anti-inflammatory Effects of Ethanol Extract from Bark of Acer barbinerve Maxim (청시닥나무 수피 에탄올 추출물의 항염증 효과)

  • Lee, Han-Na;Kim, Jin-Kyu;Kwon, Gyoo-Taik;Shim, Jae-Hoon;Kim, Jong-Dai;YoonPark, Jung-Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.9
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    • pp.1242-1247
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    • 2012
  • Acer barbinerve Maxim belongs to the Aceraceae tree family and is often consumed as an Oriental medicine. In this study, we investigated whether or not ethanol extract from the bark of A. barbinerve Max. (EBA) inhibits lipopolysaccharide (LPS)-induced inflammatory responses in Raw264.7 macrophages. EBA was fractionated using n-hexane, $CH_2Cl_2$, ethyl acetate (EtOAc), and water. Raw264.7 cells were treated with 20 ${\mu}g/mL$ of EBA and the EBA fractions. EBA inhibited LPS-induced nitric oxide (NO) production. Among the three fractions, EtOAc fraction of EBA (EFEBA) was the most effective in inhibiting LPS-induced NO production without significant cytotoxicity in Raw264.7 cells. EFEBA futher reduced LPS-induced expression of inducible NO synthase (iNOS) proteins and its corresponding mRNA. Additionally, EFEBA decreased the mRNA levels of interleukin (IL)-6, IL-$1{\beta}$, and tumor necrosis factor-${\alpha}$ in LPS-treated Raw264.7 cells. Lastly, EFEBA inhibited LPS-induced degradation of the inhibitor of kappaBalpha ($I{\kappa}B{\alpha}$) as well as phosphorylation of p65 nuclear factor-${\kappa}B$ (NF-${\kappa}B$). These results indicate that EFEBA exhibits strong anti-inflammatory effects and can be developed as a potential anti-inflammatory agent.

Inhibitory effects of ethanol extract from Vicia amoena on LPS(Lipopolysaccharide) induced nitric oxide and prostaglandin E2 production in RAW264.7 macrophage cell (갈퀴나물 에탄올 추출물의 RAW264.7 대식세포에서 LPS(Lipopolysaccharide)로 유도된 nitric oxide 및 prostaglandin E2 생성 저해효과)

  • Nam, Jung-Hwan;Park, Soo-Jin
    • Asia-pacific Journal of Multimedia Services Convergent with Art, Humanities, and Sociology
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    • v.9 no.6
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    • pp.443-450
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    • 2019
  • Vicia amoena has traditionally been used to treat disease of rheumatism, arthralgia, muscular paralysis, abscess and eczema, and it has anti-inflammatory properties. However, validity of the anti-inflammatory activity has not been scientifically in vestige acted so far. Therefore, the aim of this study was to investigate the anti-inflammatory potential of V. amoena using the ethanolic extract. To evaluate the anti-inflammatory effects, we examined the inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) on RAW264.7 cells. Our results indicated that ethanolic extract of V. amoena significantly inhibited the LPS-induced NO and PGE2 production in RAW264.7 cells. The ethanolic extract of V. amoena has inhibited the PGE2 production by 88.0±0.8 % at the concentration of 40㎍/ml. This results showed that ethanol extract of V. amoena is expected to be a good candidate for development into source of inflammation inhibitor

Quercetin Inhibits Inflammation Responses via MAPKs and NF-κB Signaling Pathways in LPS-stimulated RAW264.7 Cells (마우스 대식세포 RAW264.7 세포에서 MAPK와 NF-κB 경로를 통한 quercetin의 염증 반응 저해 활성)

  • Woo Young, Won;Jeong Tae, Kim;Keun Ho, Kim;Ji Young, Hwang;Chung-Wook, Chung;Jong Sik, Kim
    • Journal of Life Science
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    • v.32 no.11
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    • pp.899-907
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    • 2022
  • Quercetin is one of bio-flavonoids which are abundant in fruits and vegetables and has been reported to have various pharmacological potentials such as anti-oxidation, anti-inflammation, anti-cancer, and anti-virus effects. In the present study, the anti-inflammatory effects and its working molecular mecha- nism of quercetin were investigated in mouse macrophage RAW264.7 cells. Quercetin significantly inhibited nitric oxide (NO) production in a dose-dependent manner without affecting cell viability and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 cells. In addition, quercetin decreased phosphorylation of p38, JNK, and ERK, and inhibited phosphorylation of NF-κB p65 protein and its inhibitor IκBα indicating that quercetin has the anti-inflammatory effects via regulation of MAPKs and NF-κB signaling pathway. We also detected expression changes of four kinds of pro-inflammatory cytokine genes (CSF2, IL-1β, IL-6, and TNF-α) with quantitative real-time PCR. The results showed that quercetin decreased the expression of four pro-inflammatory genes in LPS-stimulated RAW264.7 cells. Overall, our results showed that quercetin effectively suppressed inflammation responses induced by LPS in RAW264.7 cells via regulating MAPK and NF-κB pathway and down-regulating the expression of pro-inflammatory cytokine genes.

Protective Effects of Chrysanthemi Indici Flos Extract and Flaxseed Oil Mixture on HCl/ethanol-induced Acute Gastric Lesion Mice (급성 위염 동물 모델에서 감국(甘菊) 추출물과 아마인유(亞麻仁油) 혼합물의 위 점막 보호 효과)

  • Lee, Jin A;Kim, Soo Hyun;Kim, Min Ju;Ahn, Jeong-Hyun;Park, Hae-Jin;Lee, Woo Rak;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.33 no.6
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    • pp.19-28
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    • 2018
  • Objectives : The objective of this study was to investigate the protective effect of Flaxseed oil and Chrysanthemi Indici Flos 50% ethanol extract in an HCl/ethanol induced acute gastritis model. Methods : ICR mice were divided into 6 groups; normal mice (Nor), gastritic mice with distilled water (Veh), gastritic mice with 10 mg/kg sucralfate (SC), gastritic mice with 16 g/㎏ Flaxseed oil (FO), gastritic mice with FO + 50 mg/kg Chrysanthemi Indici Flos (FCL), and gastritic mice with FO + 100 mg/kg Chrysanthemi Indici Flos (FCH). Then, mice were orally administered with 150 mM HCl/60% ethanol and caused acute gastritis. After 1 hr, mice were sacrificed, and blood and stomach tissue were collected. Results : Administration of FCL and FCH to mice prior to the induction of gastritis was found to reduce gastric injury. reactive oxygen species (ROS) and peroxy nitrite ($ONOO^-$) levels of stomach tissues were significantly decreased in FO, FCL, and FCH compared to Veh group. As results of stomach protein analyses, FCL and FCH effectively reduce inflammatory-related factors such as inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and interleukin 1 beta ($IL-1{\beta}$) in gastric lesion mice. In addition, nuclear factor kappa B p65 ($NF-{\kappa}B$ p65) and phosphorylation inhibitor of nuclear factor kappa $B{\alpha}(p-I{\kappa}B{\alpha})$ were down-regulated in FCL and FCH administrated gastric lesion mice. Conclusions : These results suggest that FCL and FCH has an inhibitory effect against gastric injury. Therefore, FCL and FCH has the potential to be used as a natural therapeutic drug.

Anti-inflammation effect of rebaudioside A by inhibition of the MAPK and NF-κB signal pathway in RAW264.7 macrophage (RAW264.7 대식세포에서 MAPK 및 NF-κB 신호전달 억제를 통한 rebaudioside A의 항염 효과)

  • Choi, Da Hee;Cho, Uk Min;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.61 no.2
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    • pp.205-211
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    • 2018
  • Rebaudioside A is a natural sweetener isolated from Stevia rebaudiana Bertoni, one of the glycosides based on steviol. Recent studies have shown that rebaudioside A inhibits the inflammatory response by inhibiting cytokines secretion such as interleukin-$1{\alpha}/1{\beta}$ in activated RAW264.7 mouse macrophage cells by LPS. However, the inhibitory mechanism of inflammation by rebaudioside A in the presence of LPS has not been fully elucidated. Therefore, in this study, we tried to investigate the anti-inflammatory activity of rebaudioside A at the protein level when RAW264.7 cells were stimulated by LPS. The inducible nitric oxide synthase protein expression level was reduced in the group treated with $250{\mu}M$ rebaudioside A compared to the LPS-treated group. In addition, the mRNA expression level of $NF-{\kappa}B$, which is a representative nuclear transcription factor by inflammatory signal, was also decreased as compared with that of LPS-treated group. In addition, $NF-{\kappa}B$ and inhibitor-${\kappa}B$ ($I-{\kappa}B$) complexes that are known to be dissociated by $I-{\kappa}B$ phosphorylation and ubiquitination were less phosphorylated than LPS treated group in the presence rebaudioside A. Finally, we could find that rebaudioside A was involved in the $NF-{\kappa}B$ pathway through reducing extracellular signal-regulated kinase1/2 phosphorylation in a concentration-dependent manner. These results suggest that rebaudioside A might suppress inflammatory reaction through MAPK and $NF-{\kappa}B$ regulation in LPS-stimulated RAW264.7.

Anti-Inflammatory Activity of Oligomeric Proanthocyanidins Via Inhibition of NF-κB and MAPK in LPS-Stimulated MAC-T Cells

  • Ma, Xiao;Wang, Ruihong;Yu, Shitian;Lu, Guicong;Yu, Yongxiong;Jiang, Caode
    • Journal of Microbiology and Biotechnology
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    • v.30 no.10
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    • pp.1458-1466
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    • 2020
  • Oligomeric proanthocyanidins (OPCs), classified as condensed tannins, have significant antioxidation, anti-inflammation and anti-cancer effects. This study was performed to investigate the anti-inflammatory effects of OPCs and the mechanism underlying these effects in lipopolysaccharide (LPS)-stimulated bovine mammary epithelial cells (MAC-T). Real-time PCR and ELISA assays indicated that OPC treatment at 1, 3 and 5 ㎍/ml significantly reduced the mRNA and protein, respectively, of oxidant indicators cyclooxygenase-2 (COX-2) (p < 0.05) and inducible nitric oxide synthase (iNOS) (p < 0.01) as well as inflammation cytokines interleukin (IL)-6 (p < 0.01), IL-1β (p < 0.01) and tumor necrosis factor-α (TNF-α) (p < 0.05) in LPS-induced MAC-T cells. Moreover, OPCs downregulated LPS-induced phosphorylation of p65 and inhibitor of nuclear factor kappa B (NF-κB) (IκB) in the NF-κB signaling pathway (p < 0.01), and they inhibited p65 translocation from the cytoplasm to the nucleus as revealed by immunofluorescence test and western blot. Additionally, OPCs decreased phosphorylation of p38, extracellular signal regulated kinase and c-jun NH2-terminal kinase in the MAPK signaling pathway (p < 0.01). In conclusion, the anti-inflammatory and antioxidant activities of OPCs involve NF-κB and MAPK signaling pathways, thus inhibiting expression of pro-inflammatory factors and oxidation indicators. These findings provide novel experimental evidence for the further practical application of OPCs in prevention and treatment of bovine mastitis.