• Nutrition Research and Practice
• /
• v.11 no.2
• /
• pp.90-96
• /
• 2017

BACKGROUND/OBJECTIVES: Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. METHODS/MATERIALS: Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and $30{\mu}M$ lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B ($NF-{\kappa}B$), inhibitor kappa B ($I{\kappa}B$), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) were determined via enzyme-linked immunosorbent assays. RESULTS: In cells treated with lycopene and LPS, the mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P < 0.05). The concentrations of $PGE_2$ and NO decreased according to the lycopene concentration (P < 0.05). The protein expressions of $NF-{\kappa}B$ and JNK were decreased significantly according to lycopene concertation (P < 0.05). CONCLUSIONS: Lycopene restrains $NF-{\kappa}B$ and JNK activation, which causes inflammation, and suppresses the expression of $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, COX-2, and iNOS in SW480 human colorectal cancer cells.

• BMB Reports
• /
• v.38 no.6
• /
• pp.633-638
• /
• 2005

Biosynthesis of prostanoids is regulated by three sequential enzymatic steps, namely phospholipase $A_2$ enzymes, cyclooxygenase (COX) enzymes, and various lineage-specific terminal prostanoid synthases. Prostaglandin E synthase (PGES), which isomerizes COX-derived $PGH_2$ specifically to $PGE_2$, occurs in multiple forms with distinct enzymatic properties, expressions, localizations and functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein that is markedly induced by proinflammatory stimuli, is down-regulated by anti inflammatory glucocorticoids, and is functionally coupled with COX-2 in marked preference to COX-1. Recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate $PGE_2$ production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes.

• Biomolecules & Therapeutics
• /
• v.19 no.1
• /
• pp.52-58
• /
• 2011

The inhibitory effect of Chung-Jang-Hwan (C-mix) consisted of Geranium nepalense subsp. thunbergii, Saururus chinensis, and Rubus coreanus were investigated in dextran sulfate sodium (DSS)-induced colitic mice by microarray analysis. Treatment with Cmix improved colitic symptoms, including colon shortening and myeloperoxidase activity. Treatment with DSS alone upregulated the expression levels of inflammation-related genes, including IL-$1\beta$, IL-6, CCL2, CCL4, CCL5, CCL7, CCL8, CCL24, CXCL1, CXCL2, CXCL5, CXCL9 and CXCL10, and other colitis-related genes such as COX-2, PAP, MMP family, S100a8, S100a9 and DEFA1 in mice. However, treatment with C-mix inhibited the expression levels of inflammation-associated genes induced by DSS. The increased expression levels of COX-2 and IL-$1\beta$, representative inflammatory genes, were confirmed by a quantitative realtime polymerase chain reaction analysis. These results indicate that C-mix may ameliorate colitis by the inhibitory regulation of inflammation-associated genes.

• Journal of Mushroom
• /
• v.13 no.4
• /
• pp.330-333
• /
• 2015

This study was carried out to compare the anti-inflammation effects of various fruiting body of Ganoderma species and Cordyceps militaris, Phelinus linteus extracts. We concentrated Ganoderma species and other medicinal mushrooms by extracting with ethanol. And We made it $100{\mu}g/ml$ concentration. As a result of nitrite scavenging activity, in the contrast to the positive control; Ascorbic acid was 25%, ASI 7080 of Ganoderma species was disappeared up to around 40%. And in the contrast to Ascorbic acid was 55%, ASI 7002 was 78.5% that was the highest anti-inflammation effect in the result of "No assay test". The Cordyceps militaris showed 75% and Hericium erinaceus showed 59.7% of anti-inflammation effect. As a result of the fungus yield control test of $TNF-{\alpha}$ through ELISA method to ASI 7002 of Ganoderma species that showed the highest anti-inflammation, it was reduced as same as LPS non-treatment. We extracted RNA from ASI 7002 Ganoderma species 10, 50, $100{\mu}g/ml$ concentration and LPS $10{\mu}g/ml$ of Raw 264.7 cell. And we tested the expression of iNOS, COX-2 and TNF-a that are kinds of inflammation gene after synthesizing RNA with cDNA. Finally we could find that iNOS, COX-2 and TNF-a were all controlled expression in the result of above experiment.

• Journal of Acupuncture Research
• /
• v.21 no.3
• /
• pp.121-131
• /
• 2004

Objective : The purpose of this study was investigation how the bee venom(BV) prevents inflammation in human cell. Methods : we induced inflammation on human synoviocyte cell by lipopolysaccharide(LPS) and sodium nitroprusside(SNP), treated the bee venom and melittin on this cell, surveyed the expression of Nisotric oxide(NO), inducible nitric oxide synthase(iNOS), Cyclooxygenease-2(COX-2), cytolic phospholipase $A_2(cPLA_2)$, Prostaglandin $E_2(PGE_2)$ and nuclear factor-${\kappa}B$(NF-${\kappa}B$), and got below conclusions. Results : Compared with control 1. Expressions of LPS-induced $PGE_2$(BV 1, $5{\mu}g/m{\ell}$) and SNP-induced PGE2(BV 0.5, 1, $5{\mu}g/m{\ell}$)were decreased significantly. 2. Expressions of LPS-induced NO(BV 0.5, 1, $5{\mu}g/m{\ell}$) and SNP-induced NO(BV 1, $5{\mu}g/m{\ell}$)were decreased significantly. 3. Expressions of LPS-induced COX-2(BV 1, $5{\mu}g/m{\ell}$) and SNP-induced COX-2(BV $5{\mu}g/m{\ell}$)were decreased significantly. 4. Expressions of LPS-induced iNOS(BV 0.5, 1, $5{\mu}g/m{\ell}$) and SNP-induced iNOS(BV $5{\mu}g/m{\ell}$) were meanless by all dose. 5. Expressions of LPS-induced $cPLA_2$(BV 1, $5{\mu}g/m{\ell}$) and SNP-induced cPLA2(BV 1, $5{\mu}g/m{\ell}$)were decreased significantly. 6. Expressions of LPS-induced NF-${\kappa}B$(BV $5{\mu}g/m{\ell}$, melittin $5{\mu}g/m{\ell}$) and SNP-induced NF-${\kappa}B$(BV 0.5, 1, $5{\mu}g/m{\ell}$, melittin 5, $10{\mu}g/m{\ell}$)were decreased significantly. 7. Expressions of LPS-induced NF-${\kappa}B$ binding activity (BV $1{\mu}g/m{\ell}$, melittin $5{\mu}g/m{\ell}$, melittin $5{\mu}g/m{\ell}$+ DTT 20mM) were decreased significantly. Conclusion : The bee venom treatments on synoviocyte showed significant changes in LPS and SNP induced NO, iNOS, COX-2, cPLA2, PGE2 and NF-${\kappa}B$, these results suggest that bee venom is effective to inflammations and establish the process of bee venom therapy, so we expect active use of bee venom to control the inflammation.

• Nutrition Research and Practice
• /
• v.9 no.2
• /
• pp.123-128
• /
• 2015

BACKGROUND/OBJECTIVES: Natural products or active components with a protective effect against oxidative stress have attracted significant attention for prevention and treatment of degenerative disease. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from Litchi chinensis Sonn. We investigated the protective effect and its related mechanism of oligonol against oxidative stress. MATERIALS/METHODS: Oxidative stress in C6 glial cells was induced by hydrogen peroxide ($H_2O_2$) and the protective effects of oligonol on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) synthesis, and mRNA expression related to oxidative stress were determined. RESULTS: Treatment with oligonol inhibited NO and ROS formation under cellular oxidative stress in C6 glial cells. In addition, it recovered cell viability in a dose dependent-manner. Treatment with oligonol also resulted in down-regulated mRNA expression related to oxidative stress, nuclear factor kappa-B (NF-${\kappa}B$) p65, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the control group treated with $H_2O_2$. In particular, expression of NF-${\kappa}B$ p65, COX-2, and iNOS was effectively reduced to the normal level by treatment with $10{\mu}g/mL$ and $25{\mu}g/mL$ of oligonol. CONCLUSIONS: These results indicate that oligonol has protective activity against oxidative stress-induced inflammation. Oligonol might be a promising agent for treatment of degenerative diseases through inhibition of ROS formation and NF-${\kappa}B$ pathway gene expression.

• Natural Product Sciences
• /
• v.3 no.1
• /
• pp.19-28
• /
• 1997

Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible cyclooxygenase (COX-II) is induced by some cytokines, mitogens, and endotoxin presumably in pathological conditions such as inflammation. We have evaluated the inhibitory effects of solvent fractionated extracts of natural products on the activities of COX-I and COX-II. Oxygen uptake COX assay was performed, as a primary screening from the tissue extracts of bovine seminal vesicles (BSV), by monitoring the initial rate of oxygen uptake using an oxygen electrode. Additionally, we evaluated plant extracts for the inhibitory effects of COX-I (in HEL cells) and COX-II (in lipopolysaccharide activated J774A.1 macrophages) using thin layer chromatography of prostanoids produced from $^{14}C-labelled$ arachidonic acid (AA). The use of such models of COX-I and COX-II assay will lead to the identification of specific inhibitors of cyclooxygenases with presumably less side effects than present therapies. Inhibitory effects of 50 kinds of plant extracts on the COX-I and COX-II activities were determined and the active fractions were found in the ethyl acetate fractions of Dryopteris crassirhizoma (roots), Amomum cardamomum (roots), Triticum aestivum (seeds), Perilla sikokiana (leaves), Anemarrhena asphodeloides (roots). Especially, the ethyl acetate fraction of Dryopteris crassirhizoma (roots), which exhibited the strong inhibition against BSV COX $(IC_{50},\;65.4\;{\mu}g/ml)$, COX-I $(IC_{50},\;8.5\;{\mu}g/ml)$, and COX-II $(IC_{50},\;17.2\;{\mu}g/ml)$, is under investigation to isolate active principles using activity-guided fractionation method.

• Microbiology and Biotechnology Letters
• /
• v.50 no.3
• /
• pp.354-360
• /
• 2022

This research was designed to evaluate the possible anti-inflammatory effects of Carex scabrifolia Steud. extract using RAW264.7 cells. The assessments of these effects were based on cell viability assay, mRNA expression levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNFα), and levels of nitric oxide (NO)/prostaglandin E2 (PGE₂) production. Quantitative real-time polymerase chain reaction showed that treatment with C. scabrifolia Steud. extract decreased the mRNA levels of iNOS, COX2, IL-1α, IL-1β, IL-6, and TNFα. Furthermore, from the production levels of PGE₂/NO, it can be inferred that C. scabrifolia Steud. extract exhibited anti-inflammatory properties. These results suggest that C. scabrifolia Steud. extract contains anti-inflammatory compound(s), and consequently, that it may have applications as a potent cosmeceutical material.

• Tuberculosis and Respiratory Diseases
• /
• v.56 no.6
• /
• pp.638-645
• /
• 2004

Background : Uteroglobin is a protein produced by the normal bronchial epithelium and its expression level is lower in non-small cell lung cancer tissues and cell lines. It mainly functions as an anti-inflammatory, and when it is overexpressed in cancer cells, the neoplastic phenotype is antagonized. cPLA2 and COX-2, which are also associated with inflammation, were reported to be related to cancer. The relationship between cPLA2, COX-2 and uteroglobin is unclear. The relationship between uteroglobin and ERK, which is related to cell growth, is also not unclear. This study investigated the changes in the cPLA2 and COX-2 expression levels and the ERK activities after the overexpression of uteroglobin in non-small cell lung cancer cell lines. Methods : The A549 and NCI-H460 cell lines were infected by adenovirus-null and adenovirusuteroglobin. The cChange in the cPLA2, COX-2 expression level and ERK activity after uteroglobin overexpression was measured by Western blot. The change in MMP activity was measured by zymography. Results : Western blot revealed decreased expression levels of cPLA2, and COX-2, and increased pERK levels in nonsmall cell lung cancer cells after uteroglobin overexpression. Zymography revealed no changes in the MMP-2 activity and lower MMP-9 activity. U0126, which is a specific inhibitor of ERK-activating kinase MEK-1/-2, prevented the decrease in the MMP-9 activity Conclusions : A decrease in cPLA2 expression, COX-2 expression, MMP-9 activity and a increase in ERK activity may be related to the anticancer effects of uteroglobin in nonsmall cell lung cancer cells.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.19 no.6
• /
• pp.1568-1572
• /
• 2005

Polycyclic aromatic hydrocarbon (PAH), such as benzo(a)pyrene (B(a)P), are toxic environmental contaminants known to enhance oxidative stress, production of pro-inflammatory and inflammatory cytokines. The present study was designed in order to determine whether wild ginseng (Panax ginseng C. A. Meyer) protect PAH-induced oxidative stress and inflammation. B(a)P (0.5 mg/kg, i.p.) treatment increased the distribution of immunoreactive cells for tumor necrosis factor $(TNF)-\alpha$ and cyclooxygenase (COX)-2 in peri-portal triad region and immunoreaction was shown in the cytoplasm of macrophage. Pre-treatment with wild ginseng significantly decreased immune responses in the rats treated with B(a)p. The rats given 50 mg/kg/day for 4 weeks before B(a)P treatment had 1.39-fold and 1.5-fold inhibition of $TNF-\alpha$ and COX-2 positive reaction, respectively. Wild ginseng extract alone had no effect on the distributional changes. The SOD activity as scavenger enzymes after wild ginseng administration dose-dependantly increased compared with butylated hydroxytoluene, a general radical scavenger. These data likely indicate that wild ginseng extract may act as inflammatory regulator in conjunction with inhibition of oxidant dependent metabolic activation in environmental contaminants-induced hepatic inflammation.