• Title/Summary/Keyword: COX-2 inhibition

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Anti-inflammatory Effect of Branches Extracts from Quercus mongolica in LPS-induced RAW264.7 Cells

  • Eo, Hyun Ji;Park, Youngki;Kang, Jin Taek;Park, Gwang Hun
    • Korean Journal of Plant Resources
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    • v.32 no.6
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    • pp.698-704
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    • 2019
  • Quercus mongolica (QM), which belongs to fagaceae, is one of the oak native to Korea. We evaluated the anti-inflammatory effect of branches extracted with 70% ethanol of QM (QM-B) and elucidated the potential signaling pathway in LPS-induced RAW264.7 cells. The QM-B showed anti-inflammatory activity through inhibition of NO production. The QM-B dose-dependently suppressed NO production by inhibiting iNOS, COX-2 and IL-6 expression in LPS-induced RAW264.7 cells. The QM-B inhibited the degradation and phosphorylation of IκB-α and NF-κB activation. The QM-B suppressed the phosphorylation of p38 and ERK1/2. Also, the QM-B increased HO-1 expression. These results suggested that QM-B may utilize anti-inflammatory activity by suppressing NF-κB and MAPK signaling pathway and inducing HO-1 expression indicated that the QM-B can be used as a natural anti-inflammatory drugs.

Immune-Enhancing Effects of Green Lettuce (Lactuca sativa L.) Extracts through the TLR4-MAPK/NF-κB Signaling Pathways in RAW264.7 Macrophage Cells

  • Seo, Hyun-Ju;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.33 no.3
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    • pp.183-193
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    • 2020
  • Recently, as a natural substance has been emphasized interest in research to enhance the immune function. Green lettuce (Lactuca sativa L.) is a popular vegetable used fresh and it contains various phytochemicals and antioxidant compounds, and has been reported to have various physiological activities such as antibacterial, antioxidant, antitumor and anti-mutagenic. However, only a few studies have investigated on the mechanism of action of immune-enhancing activity of lettuce. Therefore, in this study, the immunomodulatory activities and potential mechanism of action of Green lettuce extracts (GLE) were evaluated in the murine macrophage cell line RAW264.7. GLE significantly increased NO levels by RAW264.7 cells, as well as expressions of immunomodulators such as iNOS, COX-2, IL-1β, IL-6, IL-12, TNF-α and MCP-1. Although GLE activated ERK1/2, p38, JNK and NF-κB, GLE-mediated expressions of immunomodulators was dependent on p38, JNK and NF-κB. In addition, TLR4 inhibition blocked GLE-mediated expressions of immunomodulators and activation of p38, JNK and NF-κB. Taken together, these results demonstrated that TLR4-MAPK/NF-κB signalling pathways participated in GLE-induced macrophage activation and GLE could be developed as a potential immunomodulating functional food.

Standardized microwave extract of Sappan Lignum exerts anti-inflammatory effects through inhibition of NF-κB activation via regulation of heme oxygenase-1 expression

  • Md Anisuzzaman Chowdhury;Moonbum Choi;Wonmin Ko;Hwan Lee;Sam Cheol Kim;Hyuncheol Oh;Eun‑Rhan Woo;Youn‑Chul Kim;Dong‑Sung Lee
    • Molecular Medicine Reports
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    • v.19 no.3
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    • pp.1809-1816
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    • 2019
  • The extract of Sappan Lignum, the heartwood of Caesalpinia sappan L., has been used in medicine to improve blood circulation. Recently, the application of microwave extraction methods has been a major focus of research into the extraction of components from natural sources. In this experiment, we compared the anti-inflammatory effects of Sappan Lignum prepared by heat-70% EtOH extraction (CSE-H-70E) and microwave-70% EtOH extraction (CSE-MW-70E). High-performance liquid chromatography analysis was used to identify the compounds in these extracts. The heat-70% EtOH and microwave-70% EtOH extracts of Sappan Lignum had different chromatograms. CSE-MW-70E significantly inhibited the protein expression of iNOS and COX-2, PGE2, TNF-α, and reduced NO and IL-1β production in macrophages exposed to LPS, whereas, only high concentrations of CSE-H-70E (20 ㎍/ml) resulted in any effects. Furthermore, CSE-MW-70E upregulated heme oxygenase-1 (HO-1) expression. In addition, the use of tin protoporphyrin, an inhibitor of HO-1, confirmed the inhibitory effects of CSE-MW-70E on pro-inflammatory mediators. These results suggested that the CSE-MW-70E-mediated upregulation of HO-1 played an important role in the anti-inflammatory effects of macrophages. Therefore, these findings showed that microwave extraction can be utilized to improve the extraction efficiency and biological activity of Sappan Lignum.

Inhibitory Activity of Cordyceps bassiana Extract on LPS-induced Inflammation in RAW 264.7 Cells by Suppressing NF-κB Activation

  • Yoon, Deok Hyo;Han, Changwoo;Fang, Yuanying;Gundeti, Shankariah;Han Lee, In-Sook;Song, Won O;Hwang, Ki-Chul;Kim, Tae Woong;Sung, Gi-Ho;Park, Haeil
    • Natural Product Sciences
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    • v.23 no.3
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    • pp.162-168
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    • 2017
  • Cordyceps bassiana has long been used as an oriental medicine and reported to possess diverse biological activities. The fruiting bodies of Cordyceps bassiana was extracted with ethanol and then further fractionated with n-hexane, ethyl acetate, n-butanol and water. The butanol fraction from Cordyceps bassiana (CBBF) exhibited the most effective in anti-inflammatory activity in RAW 264.7 macrophages and the roles of CBBF on the anti-inflammation cascade in LPS-stimulated RAW 264.7 cells were studied. To investigate the mechanism by which CBBF inhibits NO, iNOS and COX-2, the activation of $I{\kappa}B$ and MAPKs in LPS-activated macrophage were examined. Our present results demonstrated that CBBF inhibits NO production and iNOS expression in LPS-stimulated RAW 264.7 macrophage cells, and these effects were mediated through the inhibition of $I{\kappa}B-{\alpha}$, JNK and p38 phosphorylation. Also, CBBF suppressed activation of MAPKs including p38 and SAPK/JNK. Furthermore, CBBF significantly suppressed LPS-induced intracellular ROS generation. Its inhibition on iNOS expression, together with its antioxidant activity, may support its anti-inflammatory activity. Thus Cordyceps bassiana can be used as a useful medicinal food or drug for further studies.

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.

High-mobility Group Box 1 Induces the Epithelial-mesenchymal Transition, Glycolytic Switch, and Mitochondrial Repression via Snail Activation (HMGB1/Snail cascade에 의한 epithelial-mesenchymal transition 및 glycolytic switch, mitochondrial repression 유도)

  • Lee, Su Yeon;Ju, Min Kyung;Jeon, Hyun Min;Kim, Cho Hee;Park, Hye Gyeong;Kang, Ho Sung
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1179-1191
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    • 2019
  • Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.

Immunostimulatory and Anti-Obesity Activity of Lonicera insularis Nakai Extracts in Mouse Macrophages RAW264.7 Cells and Mouse Adipocytes 3T3-L1 Cells (섬괴불나무(Lonicera insularis Nakai) 추출물의 면역자극 및 항비만 활성)

  • Yu, Ju Hyeong;Yeo, Joo Ho;Choi, Min Yeong;Lee, Jae Won;Geum, Na Gyeong;An, Mi-Yun;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.35 no.4
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    • pp.417-427
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    • 2022
  • In this study, we investigated in vitro immuno-stimulatory and anti-obesity activity of fruit (LIF), leaves (LIL) and stems (LIS) from Lonicera insularis Nakai in mouse macrophages RAW264.7 cells and mouse pre-adipocytes 3T3-L1 cells. LIF, LIL and LIS increased the production of immunostimulatory factors such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and activated phagocytosis in RAW264.7 cells. Inhibition of toll-like receptor 2/4 (TLR2/4) partly blocked LIF, LIL and LIS mediated production of immunostimulatory factors. In addition, inhibition of mitogen-activated protein kinases (MAPK) signaling attenuated the production of immunostimulatory factors induced by LIF, LIL and LIS. Based on these results of this study, LIF, LIL and LIS is thought to activate macrophages the production of immunostimulatory factors and phagocytosis through toll-like receptor 2/4 (TLR2/4) and MAPKs signaling pathway. In anti-obesity study, LIF reduced the lipid accumulation in 3T3-L1 cells. LIF increased the protein phosphorylation expressions such as AMP-activated protein kinase (AMPK), hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL) related to the lipolysis of the adipocytes. In addition, LIF increased the expression of proteins involved in energy metabolism and brown adipose tissues differentiation such as peroxisome proliferator-activated receptor gamma coativator 1α (PGC-1α) and PR domain-containing16 (PRDM16). These results suggest that LIF is involved in lipid accumulation inhibition through expressing the proteins such as lipolysis and differentiation of white adipocytes to brown adipocytes.

Modulation of Nrf2/ARE and Inflammatory Signaling Pathways by Hericium erinaceus Mycelia Extract

  • Jin, Kyong-Suk;Park, Ji-Young;Cho, Mi-Kyung;Jang, Ji-Hyun;Jeong, Jae-Han;Ok, Seon;Bak, Min-Ji;Song, Young-Sun;Kim, Myo-Jeong;Cho, Chung-Won;Jeong, Woo-Sik
    • Food Science and Biotechnology
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    • v.18 no.5
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    • pp.1204-1211
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    • 2009
  • Hericium erinaceus is an edible mushroom used as a medicinal food in Asian countries. In this study, the chemopreventive effects of H. erinaceus mycelia hot water extract (HEW) were evaluated. HEW remarkably induced the luciferase activity of the antioxidant response element (ARE), located in the promoter region of phase 2 and antioxidant genes and regulated by nuclear factor E2-related factor 2 (Nrf2). The up-regulation of ARE activity by HEW corresponded with the induction of Nrf2 and the antioxidant enzyme, hemeoxygenase-1. The inhibition of cyclooxygenase-2 (COX-2) activity is a promising effective approach in cancer chemoprevention, and HEW prominently suppressed COX-2 protein expression in HepG2 cells. Furthermore, HEW showed anti-inflammatory activity by modulating inflammatory mediators such as nitric oxide (NO), inducible NO synthase, tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and the transcription factor, nuclear factor-${\kappa}B$, in lipopolysaccharide-stimulated RAW 264.7 cells. These results suggest that H. erinaceus possessed anti-tumor and anti-inflammatory effects via the modulation of Nrf2/ARE and inflammatory signaling pathways, and may therefore have potential use as a natural chemopreventive agent.

Antiinflammatory Activity of Solvent-partitioned Fractions from Atriplex gmelinii C. A. Mey. in LPS-stimulated RAW264.7 Macrophages (염생식물 가는갯는쟁이 용매 추출물의 항염증활성)

  • Jeong, Heejeong;Kim, Hojun;Ju, Eunsin;Lee, Seul-Gi;Kong, Chang-Suk;Seo, Youngwan
    • 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.

Photoprotective Effect of Grape Pruning Stem Extracts on the UVB Induced HR-1 Mice Skin (포도전정가지 추출물이 UVB에 유도된 HR-1 mice의 피부손상에 대한 광보호 효과)

  • Kim, Joung-Hee;Kim, Jong Guk;Kim, Sun-Gun;Jeong, Seung-IL;Jang, Min-Jung;Kim, Kil-Soo;Kim, Keuk-Jun;Kwack, Seung-Jun
    • Journal of Life Science
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    • v.27 no.4
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    • pp.383-389
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    • 2017
  • This study intends to analyze the contents of rutin, procyanidin B3, quercetin, kaempferol, known to have antioxidant, anti-inflammatory and anti-carcinogenic effects, among the polyphenol type contained in the grape pruning stem extracts (GPSE), utilizing grape stems being discarded after harvest, measure the effects on the skin moisture, inhibition of skin cell proliferation, anti-inflammatory on the damaged skin of a HR-1 mice induced with UVB, and verify the applicability as a material for functional food and functional cosmetics. The results of verifying the photoprotection effects through the skin proliferation control through of GPSE showed similar result to suncream was achieved at the GPSE concentration of 2,000 mg/kg on the epidermis (p<0.05). The results showed anti-inflammatory effects on all groups applied with GPSE as compared to the control group irradiated with UVB, but at the GPSE concentration of 1,000 mg/kg, a lower COX-2 protein expression at 8%, lower than the 22% of suncream, was observed to achieve an excellent anti-inflammatory effect (p<0.05). The results of this study confirmed the existence of active polyphenol type, such as rutin, kaempferol, querocetin and procyanidin B3, within the GPSE, and GPSE has improvement effects on moisturizing effects, skin proliferation control effect, inflammatory control effect and improvement effects on the skin barrier function through UV ray damage. GPSE is a functional ingredient with a potential for skin protection effects, and has high utilization as an ingredient for functional food and functional cosmetics.