• Natural Product Sciences
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• v.10 no.6
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• pp.315-320
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• 2004

Alpha-viniferin was previously isolated as a cyclooxygenase (COX)-2 inhibitor from Carex humilis (Cyperaceae) and is an oligomeric stilbene compound with benzofuran (BF) moieties in its chemical structure. In the present study, a chemically synthetic BF compound, named as 3,3-dimethyl-2,3,4,6,7,8,9,10,11,12,13,14,15,16,17,18-hexadecahydro-1H-benzo[b] cyclopentadeca[d]furan-1-one, was discovered to inhibit bacterial lipo polysaccharide (LPS)-induced prostaglandin $E_2$ $(PGE_2)$ production in macrophages RAW 264.7. The BF compound exhibited a selectively preferred inhibitory effect on COX-2 activity over COX-1 activity. Furthermore, BF compound inhibited LPS-induced COX-2 expression at transcription level. As a down-regulatory mechanism of COX-2 expression shown by BF compound, suppression of nuclear factor $(NF)-{\kappa}B$ activation has been demonstrated. BF compound inhibited LPS-induced $NF-{\kappa}B$ transcriptional activity and nuclear translocation of $NF-{\kappa}B$ p65, in parallel, but did not affect LPS-induced degradation of inhibitory ${\kappa}B{\alpha}$ protein $(I{\kappa}B{\alpha})$. Taken together, anti-inflammatory effect of BF compound on $PGE_2$ production was ascribed by its down-regulatory action on LPS-induced COX-2 synthesis in addition to inhibitory action on enzyme activity of COX-2.

• Journal of Nutrition and Health
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• v.33 no.6
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• pp.632-638
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• 2000

This study was designed to observe the effect of green tea on colon tumor incidence and biomarkers of colon carcinogenesis in 1, 2-dimethlhydrazine-treated rats. Male Sprague Dawley rats at 7 weeks of age were divided into two groups: control and green tea(GT) groups. Control rats had distilled water as drinking water but GT group received green tea extracts(2.5%, w/v water) as drinking water throughout the experiment periods. All rats were fed the experimental diet containing 15% fat by weight for 20 weeks. and were i.m. injected with DMH for 6 weeks to give total dose of 180mg/kg body weight. Tumor incidence was reduced in GT group (39%) compared with control group (56%) Green tea significantly reduced cell proliferation (total cells per crypt, crypt length and proliferative zone) in colonic mucosa and also significantly reduced the levels of preformed prostalandin E2(PGE2) and thromboxance B2(TXB2) in colonic mucosa but the fatty acid profile of total lipid in colonic mucosa was not significantly influenced by green tea. However the relative percent of C20:4 and the levels f preformed PGE2 and TXB2. were significantly higher in tumor tissue compared with normal surrounding mucosa.Green tea increased the fecal excretion of total bile acid but not scondary bile acid which is known as one of promoters for colon cancer,. These results suggest that green tea could have preventive effect against colon cancer when consumed daily by influencing on antioxidant effect and the metabolism of arachidonic acid.

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

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1170-1176
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• 2005

2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphthoquinone[2,3-b]furan-4,9-dione (N FD-37) is a synthetic furonaphthoquinone compound. In this study, we determined that NFD-37 could inhibit the lipopolysaccharide (LPS)-induced production of inflammatory mediators in macrophages RAW 264.7. This compound inhibited LPS-induced nitric oxide (NO) or prostaglandin (PG) $E_{2}$ production in dose-dependent manners, with $IC_{50}$ values of 7.2 ${\mu}M$ and 5.3 ${\mu}m$, respectively. As the positive controls, pyrrolidine dithiocarbamate (30 ${\mu}M$) exhibited a $57{\%}$ inhibition of NO production, and NS-398 ($1{\mu}M$) manifested a $48{\%}$ inhibition of $PGE_2$ production. The inhibitory effects of NFD-37 on NO and $PGE_2$ production were determined to occur in conjunction with the suppression of inducible NO synthase or cyclooxygenase-2 expression. NFD-37 also inhibited the production of LPS-inducible tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6, at $IC_{50}$ values of 4.8-8.9 ${\mu}M$. We also determined the anti-inflammatory efficacy of NFD-37 using carrageenin-induced paw edema in experimental mice.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.

• The Korea Journal of Herbology
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• v.32 no.3
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• pp.71-78
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• 2017

Objectives : The various grape extracts derived from grape pulp, seed and skin, containing various types of polyphenols and flavonoids, have been known to have anti-inflammatory, antioxidant and improve cardiovascular condition as well as sun's damaging effects. However, there have been rare reports of various beneficial effects of grape fruit stem extract (GFSE), one of the waste products of grapes. We investigated anti-inflammatory and melanogenesis inhibitory effects of GFSE. Methods : One-hundred gram of grape fruit stem was extracted with 80% ethanol at room temperature for 3 days. After filtration, the ethanol was removed using vacuum evaporator, then lyophilized to obtain the dry extract which was stored at $-20^{\circ}C$ until used. NO levels were measured by using Greiss reagent. Prostaglandin $E_2$ ($PGE_2$) production was measured by ELISA assay. The expression levels of iNOS, COX-2, TRP-1 and TRP-2 were evaluated by western blot analysis. Results : GFSE reduced the level of nitric oxide and prostaglandin $E_2$ ($PGE_2$) production in a dose-dependent manner, compared to control. Expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein were also effectively inhibited by the GFSE. In a tyrosinase inhibitory activity, GFSE significantly reduced the tyrosinase activity and melanin content in a dose dependent manner, compared to control. GFSE also decreased the expression of tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2), known as a melanocyte-specific gene product involved in melanin synthesis. Conclusions : Therefore, these results indicated that GFSE had powerful anti-inflammatory and anti-melanogenic effects.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.1
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• pp.41-58
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• 2013

Objectives: The object of this study was to observe the in vitro anti-bacterial and anti-inflammatory effects of three single aqueous herbal extracts(Trichosanthes Semen, Gardeniae Fructus, and Angelicae Dahuricae Radix), traditionally used for treating various gynecological diseases including mastitis in Korea, against Staphylococcus aureus and lipopolysaccharide(LPS)-activated Raw 264.7 cells. Methods: Anti-bacterial activities of three single aqueous herbal extracts against S. aureus were detected using standard agar microdilution methods. In addition, the effects on the cell viability, $PGE_2$, NO, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 productions of LPS activated Raw 264.7 cells. The anti-bacterial and anti-inflammatory effects were compared with lincomycin and piroxicam, respectively in the present study. Results: MIC of three single aqueous herbal extracts against S. aureus were detected as over 25, $4.063{\pm}2.096$ and $1.641{\pm}0.972$ mg/ml, respectively. MIC of lincomycin was detected as $0.469{\pm}0.297{\mu}g/ml$ at same conditions. In addition, $ED_{50}$ against LPS-induced cell viabilities and cytokine releases of three single aqueous herbal extracts were as follows - cell viability: 7.635, 13.761, 6.986 mg/ml, NO production : 4.808, 22.015, 2.949 mg/ml, $PGE_2$ production : 3.040, 4.312, 0.821 mg/ml, TNF-${\alpha}$ production : 9.563, 54.931, 1.240 mg/ml, IL-$1{\beta}$ production : 1.362, 1.801, 0.534 mg/ml, IL-6 production : 0.371, 0.797, 0.202 mg/ml, respectively. $ED_{50}$ of piroxicam against LPS-induced cell viabilities, NO, $PGE_2$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 were detected as 35.179, 6.552, 1.162, 7.273, 7.101 and 5.044 ${\mu}g/ml$, respectively at same conditions. Conclusions: The results of the study showed anti-bacterial effects against S. aureus in the order of Gardeniae Fructus and Angelicae Dahuricae Radix aqueous extracts, except for Trichosanthes Semen. They also showed anti-inflammatory effects against LPS-activated Raw 264.7 cells in the order of Angelicae Dahuricae Radix, Trichosanthes Semen, and Gardeniae Fructus aqueous extracts. These three herbs are expected to be great substitutes to reduce side-effect of lincomycin and piroxicam, if the amount of those three single aqueous herbal extracts is adjusted appropriately.

• Journal of Nutrition and Health
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• v.34 no.8
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• pp.896-904
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• 2001

Conjugated linoleic acid(CLA) is a group of positional and geometric isomers of linoleic acid(LA) and exhibits anticarcinogenic activity in multiple experimental animal models. Cis-9,trns-11(c9t11) and trans-10,cis-12(t10c12) CLA are the principal isomers found in foods. The present study was performed to determine whether CLA and the two isomers inhibits HT-29 cell proliferation and to assess whether such an effect was related to changes in secretion of eicosanoids. Cells were incubated in serum-free medium with various concentrations(0 to 20$\mu$M) of CLA or LA. CLA inhibited cell proliferation in a dose-dependent manner, with maximal inhibition(70 $\pm$ 1%) observed at 20$\mu$M concentration after 96 hours. However, LA had no effect at the same concentration range. To compare the ability of c9f11 and t10c12 to inhibit cell proliferation, cells were incubated with increasing concentrations(0 to 4$\mu$M) of these isomers. T10c12 inhibited cell proliferation in a dose-dependent manner. A 66 $\pm$ 2% decrease in cell number was observed within 96 hours after addition of 4$\mu$M t10c12. By contrast, c9t11 had no effect. The concentrations of CLA and the two isomers in the plasma membrane were increased when they were added to the incubation medium. However, they did not alter the levels of arachidonic acid in plasma membrane. To assess whether the proliferation inhibiting effect of CLA was related to changes in eicosanoid production, prostaglandin E$_2$(PGE$_2$) and leukotriene B$_4$(LTB$_4$) concentrations in conditioned media were estimated by a competitive enzyme immunoassay. Both CLA and t10c12 increased the production of materials reactive to PGE$_2$ and LTB$_4$ antibodies in a dose-dependent manner. By contrast, c9t11 had no effect. These results indicate that inhibition of HT-29 cell proliferation by CLA is attributed to the effect of the t10v12 isomer. The materials reactive to PGE$_2$ and LTB$_4$ antibodies may inhibit growth stimulatory effect of arachidonic acid-derived eicosanoids on HT-29 cell proliferation.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.39 no.4
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• pp.303-311
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• 2013

This study was performed to investigate the anti-inflammatory activities of fermented Scutellaria baicalensis extracts using Lactobacillus rhamnosus. The extracts were WE (water extract at $100^{\circ}C$ for 24 h), EE (70% ethanol extract at $60^{\circ}C$ for 24 h), FWE (fermented and water extract at $60^{\circ}C$ for 24 h), FEE (fermented and 70% ethanol extract at $60^{\circ}C$ for 24 h). The cytotoxicity of the extracts was in the range of 11.2 ~ 15.6 % at 1.0 mg/mL concentratioin. The FEE showed the lowest activity at 1.0 mg/mL concentratioin. Compared to the WE, hyaluronidase inhibitory activity contents in the FEE increased to 9.2% at 1.0 mg/mL concentratioin. Nitric oxide production of WE, EE, FWE and FEE at 1.0 mg/mL concentration was mesured as 7.6, 7.9, 6.9, 6.4 ${\mu}M$, respectively. $PGE_2$ secretion of the human fibroblast of the FEE were lower than 810 pg/mL. Our results suggested that the extracts from fermentation process after 70% ethanol extraction had relatively high anti-inflammatory activities and that the Scutellaria baicalensis could be more extracted in FEE than others.

• Korean Journal of Animal Reproduction
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• v.26 no.2
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• pp.183-192
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• 2002

The present studies were carried out to examine the effects of exogenous oxytocin(OT) on plasma, uterine and placenta of estradiol-17$\beta$, progesterone, prostaglandin F$_2$$_{\alpha}$ (PGF$_2$$_{\alpha}$), Prostaglandin E$_2$(PGE$_2$) and OT receptor concentrations in pregnant rats. Pregnant rats received an injection of exogenous OT on days 14, 16, 18, 20, 22 of pregnancy and day 1 of postpartum. Concentrations of plasma estradiol-17 $\beta$ after OT injection started to increase after day 18 and peaked on day 22 of pregnancy but decreased on day 1 of postpartum. Plasma progesterone concentrations declined gradually from day 18 of pregnancy and decreased more rapidly until postpartum 1 day. Concentrations of estradiol-17$\beta$in uterine tissues after OT injection were sharply increased from day 20 to 22 of pregnancy and progestrone concentrations were peaked on day 16 and decreased rapidly from day 16 to 20 and maintained the same level until day 1 of postpartum. Uterine concentrations of PGF$_2$$_{\alpha}$ and PGE$_2$increased gradually until day 20 and peaked on day 22 of pregnancy but showed a marked decrease on day 1 of postpartum. Concentrations of PGF$_2$$_{\alpha}$ in placental tissues increased rapidly from day 14 of pregnancy and decreased sharply on day 1 of postpartum. Concentrations of PGE$_2$increased gradually after day 14 and peaked on day 20 of pregnancy. The concentration of OT receptor in uterus was significantly elevated from day 20 and rose to maximum on day 22 of pregnancy. These findings show that OT suppress the concentration of progestrone and stimulate productions of estradiol-17 $\beta$, PGF$_2$$_{\alpha}$, PGE$_2$ and oxytocin receptor concentrations in pregnant rats.