• The Korea Journal of Herbology
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• v.34 no.6
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• pp.117-124
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• 2019

Objective : Broccoli is edible green plant that has a wide variety of health benefits including cancer prevention and cholesterol reduction. However, leaves of broccoli are not eaten and are mostly left as waste. This study was conducted to evaluate the effects of the broccoli leaf extract (BLE) on prostaglandin E₂ (PGE₂) production related to nuclear factor kappa B (NF-κB) signaling in lipopolysaccharide (LPS)-activated macrophages. Methods : BLE was prepared by extracting dried leaf with ethanol. Cell viability was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PGE₂ and inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Expression level of each protein was monitored by Western blot analysis. Results : In LPS-activated Raw264.7 cells, PGE₂ release into culture medium was dramatically enhanced compared to control cells. However, increased PGE₂ was attenuated dose-dependently by treatment with BLE. Inhibition of PGE₂ production by BLE was due to the suppression of cyclooxygenase-2 (COX-2) expression determined by Western blot analysis. BLE also inhibited the production of inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Inhibition at PGE₂ and cytokine was mediated from inhibition of nuclear translocation of NF-κB due to the repression of inhibitory kappa B alpha (IκBα) phosphorylation and degradation. Conclusion : This study showed that BLE exerted inhibitory activities against PGE₂, which is critical for the initiation and resolution of inflammatory responses, and that inhibition of PGE₂ was mediated by suppression of NF-κB signaling. These results suggest that the waste broccoli leaves could be used for controlling inflammation.

• International Journal of Oral Biology
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• v.42 no.4
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• pp.149-153
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• 2017

Cyclooxygenase-2 (COX-2)-mediated prostaglandin $E_2$ ($PGE_2$) plays a key role in development and progression of inflammatory responses and Porphyromonas gingivalis is a common endodontic pathogen. In this study, we investigated induction of COX-2 and $PGE_2$ by P. gingivalis in human dental pulp cells (HDPCs). P. gingivalis increased expression of COX-2, but not that of COX-1. Increased levels of $PGE_2$ were released from P. gingivalis-infected HDPCs and this $PGE_2$ increase was blocked by celecoxib, a selective COX-2 inhibitor. P. gingivalis activated all three types of mitogen-activated protein kinases (MAPKs). P. gingivalis-induced activation of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) was demonstrated by the results of phosphorylation of $NF-{\kappa}B$ p65 and degradation of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$). Pharmacological inhibition of each of the three types of MAPKs and $NF-{\kappa}B$ substantially attenuated P. gingivalis-induced $PGE_2$ production. These results suggest that P. gingivalis should promote endodontic inflammation by stimulating dental pulp cells to produce $PGE_2$.

• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.86-86
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• 2001

Based on the potential inhibitors of cyclooxygenase-2 (COX-2) as anti-inflammatory or cancer chemopreventive agents, we have evaluated the active principles of COX-2 inhibition from natural products. The methanol extract of the cortex of Eugenia caryoplyllata (Myrtaceae) showed the potent inhibition of prostaglandin E$_2$(PGE$_2$) production in lipopolysaccharide (LPS)-activated RAW 264.7 cells (98.3% inhibition at the test concentration of 10 $\mu\textrm{g}$/$m\ell$) Further, hexane-soluble layer was the most active partition compared to ethyl acetate, n-butanol, and water -soluble parts. By bioassay-guided fractionation of hexane-soluble layer, eugenol was isolated and exhibited a significant suppression of PGE$_2$ production (IC$\_$50/=0.06$\mu\textrm{g}$/$m\ell$). In addition, eugenol suppressed the COX-2 gene expression in LPS-stimulated mouse macrop-hage cells. Therfore, eugenol might be a plausible lead candidate for further developing the COX-2 inhibitor as an anti-inflammatory or cancer chemopreventive agent.

• Journal of Life Science
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• v.20 no.3
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• pp.388-395
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• 2010

Cyclooxygenase (COX)-2 is generally known as an inducible enzyme, and it produces arachidonic acid to prostaglandin $E_2$ ($PGE_2$), which has been demonstrated to play a critical role in inflammation. In the present study, we investigated the effects of the extracts of fermented beans including soybean (FS), black agabean (FBA) and yellow agabean (FYA), on the expression of COXs and production of $PGE_2$ in U937 human promonocytic cells. Treatment of phorbol 12-myristate 13-acetate (PMA) significantly induced pro-inflammatory mediators such as COX-2 expression and $PGE_2$ production, whereas the levels of COX-1 remained unchanged. However, pre-treatment with FS, FBA and FYA significantly decreased PMA-induced COX-2 protein as well as mRNA, which is associated with inhibition of $PGE_2$ production. Moreover, FS, FBA and FYA markedly prevented the increase of nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$) p65 by PMA. Our data indicate that the extracts of fermented beans exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the NF-${\kappa}B$ signaling pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.1
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• pp.28-34
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• 2006

The ethanol extracts of Puerariae Radix inhibited cyclooxygenase-2 (COX-2) activity in bone marrow derived mast cells (BMMC). COX-2 is responsible for the production of large amounts of proinflammatory prostaglandins (PGs) at the inflammatory site. We have investigated the anti-inflammatory effect of ethyl acetate fraction from $70\%$ ethanol extract of Puerariae Radix (EPR), and attempted acetic acid induced writhing to verify the analgesic effect. Inflammation was induced by interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), $inteferon-\gamma$ $(IFN-\gamma)$ and lipopolysaccharide (LPS). EPR showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, prostaglandin $E_2\;(PGE_2)$ production, nitric oxide (NO) production, and matrix-metalloproteinases (MMPs) expression in mouse macrophage and rabbit articular chondrocyte. In the writhing test, EPR $(200\~400\;mg/kg)$ exhibited a dose-dependent inhibition of writhing. The results indicate that EPR have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for treating of osteoarthritis (OA).

• Journal of Life Science
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• v.19 no.10
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• pp.1396-1402
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• 2009

Hizikia fusiforme is a kind of edible brown seaweed that grows mainly in the northwest Pacific including Korea, Japan and China, and has been widely used as food in Korea. Induction of cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In this study, we investigated the effects of extracts of H. fusiforme on the expression of COX-2 and production of $PGE_2$ in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate 13-acetate (PMA) to mimic inflammation, methanol extract of H. fusiforme (MEHF) and ethanol extract of H. fusiforme (EEHF), but not water extract of H. fusiforme (WEHF), inhibited PMA-induced expression of both COX-2 protein and mRNA, which was associated with inhibition of $PGE_2$ production. To investigate the mechanism by which MEHF and EEHF inhibit COX-2 gene expression and $PGE_2$ production, we examined the activation of nuclear factor-kappaB (NF-$\kappa$B) in U937 cells. Pre-treatment with MEHF and EEHF significantly attenuated the PMA-induced IkappaB degradation and prevented nuclear translocation of NF-$\kappa$B. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-inflammatory activity of H. fusiforme.

• Archives of Pharmacal Research
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• v.27 no.6
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• pp.628-632
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• 2004

The chloroform and the ethyl acetate fractions from the roots of Acanthopanax chiisanensis exhibited a significant inhibition of prostaglandin E$_2$ (PGE$_2$）production in rat peritoneal macrophages stimulated by the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate （TPA）. Hyperin was isolated as an active principle from the ethyl acetate fraction. It sup-pressed not only $PGE_2$ production but also nitric oxide （NO） production in vitro in a concentration dependent manner. their $IC_{50}$, being 24.3 and $32.9{\;}{\mu}M$, respectively. Hyperin also caused a significant inhibition of increase in acetic acid-induced vascular permeability in mice in vivo.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

• Journal of Pharmacopuncture
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• v.20 no.3
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• pp.207-212
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• 2017

Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.