• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.105-112
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• 2003

Selective COX (cyclooxygenase)-2 inhibitors including celecoxib have been shown to induce apoptosis and cell cycle changes in various tumor cells. New inhibitors are recently being developed as chemomodulating agents. We evaluated celecoxib and screened 150 synthetic compounds for anti-proliferative activities in vitro. Effects of celecoxib on COX activity, cell growth, cell cycle distribution, and apoptosis induction were determined in A549 COX-2 overexpressing human non-small cell lung cancer (NSCLC) cells. The COX inhibition of celecoxib increased with concentration up to 82% at $1\;{\mu}M$ after 24 hr exposure. Forty ${\mu}M$ and $50\;{\mu}M$ of ce1ecoxib induced $G_1$ arrest, and TUNEL-positive apoptotic cells, respectively. Among 150 compounds, several compounds were selected for having greater COX-2 inhibitory activity and higher selectivity than celecoxib with growth inhibitory activity. Celecoxib showed concentration-dependent COX inhibitory activity, and ability to induce cell cycle arrest and apoptosis in human NSCLC cells in vitro. Among synthetic analogues screened, several compounds showed promising in vitro activity as COX-2 inhibitory anticancer agents, which warrant further evaluation in vitro and in vivo.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.82-86
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• 2008

The fruits of Gardenia jasminoides Ellis have been previously reported to possess anti-inflammatory activity. In this study, the constituents including geniposide, geniposidic acid, genipin and crocin were evaluated for their effects on prostaglandin and NO production in an attempt to establish anti-inflammatory cellular mechanisms. Among the constituents tested, only genipin significantly inhibited cyclooxygenase-2-mediated $PGE_2$ and inducible nitric oxide synthase-mediated NO production from lipopolysaccharide-treated RAW 264.7 cells at 10-100 ${\mu}$M. Genipin also inhibited nuclear transcription factor-${\kappa}B$ activation. Moreover, genipin showed in vivo antiinflammatory activity on ${\lambda}$-carrageenan-induced paw edema in mice (10.4-29.9% inhibition at 20-100 mg/kg, i.p.). All of these results suggest that genipin may contribute to anti-inflammatory activity of the fruits of G. jasminoides and an inhibitory action on prostaglandin and NO production is, at least, the part of anti-inflammatory mechanism of genipin.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.86-91
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• 2009

In our ongoing search for biological components from the Korea endemic plants, the MeOH extract of Ailanthus altissima leaves (Simaroubaceae) showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2$ ($PGD_2$) and leukotriene $C_4$ ($LTC_4$) in mouse bone marrow-derived mast cells (BMMCs). In further study, eight compounds, squalene (1), ${\beta}$-sitosterol (2), scopoletin (3), quercetin (4), luteolin (5), astragalin (6), scopolin (7), and daucosterol (8) were isolated, the chemical structures were elucidated on the basis of physicochemical and spectroscopic data and by comparison with those of published literatures. Among the compounds, 2, 4, and 5 strongly inhibited both the COX-2-dependent PGD2 generation with $IC_{50}$ values of 2.6, 7.3 and 2.5 ${\mu}M$, respectively and the generation of $LTC_4$ in the 5-LOX dependent phase with $IC_{50}$ values of 2.0, 5.1 and 1.8 ${\mu}M$, respectively, which suggest that the anti-inflammatory activity of A. altissima might occur in part via the inhibition of both $PGD_2$ and $LTC_4$ generation by 2, 4 and 5.

• Food Science and Biotechnology
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• 제18권1호
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• pp.143-149
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• 2009

The aim of this study was to elucidate the anti-inflammatory activity of safflower (Carthamus tinctorius L.) ethanolic extract fractions (CFEFs). Butanol fraction had the strongest antioxidant activity, and all CFEFs, except for chloroform fraction, partly inhibited lipopolysaccharide (LPS)-induced nitrite production in RAW 264.7 cells. In the cell-free system, hexane and butanol fractions chemically quenched nitric oxide (NO). In addition, the iNOS mRNA transcription was suppressed by ethanol extract and hexane fraction in LPS-stimulated RAW 264.7 cells. Taken together, the inhibitory effect of CFEFs on NO production from LPS-stimulated RAW 264.7 cells, might be due to both the chemical NO quenching activity and the suppression of iNOS mRNA transcription partially. The synthesis of prostaglandin $E_2$ ($PGE_2$) was potently inhibited by ethanol extract to below basal label, and the transcription of cyclooxygenase-2 (COX-2), an enzyme involving in $PGE_2$ synthesis, was partially suppressed by ethanol extract and hexane fraction. Based on these results, CFEFs may be useful as an alternative medicine for the relief and retardation of immunological inflammatory responses through the reduction of inflammatory mediators, including NO and $PGE_2$ production.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.874-878
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• 2006

Methyl gallate (MG) is a medicinal herbal product that is isolated from Paeonia lactiflora that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin $D_2\;(PGD_2)$ generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an $IC_{50}$ values of $17.0\;{\mu}M$. This compound also found inhibited the COX-2-dependent conversion of the exogenous arachidonic acid to $PGD_2$ in a dose-dependent manner with an $IC_{50}$ values of $190\;{\mu}M$, using a COX enzyme assay kit. However, at concentrations up to $80\;{\mu}M$, MG did not inhibit COX-2 protein expression in BMMC, indicating that MG inhibits COX-2 activity directly. Furthermore, MG consistently inhibited the production of leukotriene $C_4\;(LTC_4)$ in a dose dependent manner, with an $IC_{50}$ value of $5.3\;{\mu}M$. These results demonstrate that MG has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity, which might provide the basis for novel anti-inflammatory drugs.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.200-200
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• 2002

• The Korean Journal of Physiology and Pharmacology
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• 제10권1호
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• pp.45-50
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• 2006

Melittin-induced pain model has been known to be very useful for the study of pain mechanism. Melittin-induced nociceptive responses are reported to be modulated by the changes in the activity of excitatory amino acid receptor, calcium channel, spinal serotonin receptor and extracellular signaling-regulated kinase. The present study was undertaken to investigate the role of cyclooxygenase (COX) in the melittin-induced nociception. Changes in mechanical threshold, flinchings and paw thickness were measured before and after intraplantar injection of melittin in the rat hind paw. Also studied were the effects of intraperitonealy administered diclofenac (25 mg & 50 mg/kg), piroxicam (10 mg & 20 mg/kg) and meloxicam (10 mg & 20 mg/kg) on the melittin-induced nociceptions. Intraplantar injection of melittin caused marked reduction of mechanical threshold that was dose-dependently attenuated by non-selective COX inhibitor (diclofenac) and selective COX-1 inhibitor (piroxicam), but not by COX-2 inhibitor (meloxicam). Melittin-induced flinchings were strongly suppressed by non-selective COX and COX-1 inhibitor, but not by COX-2 inhibitor. None of the COX inhibitors had inhibitory effects on melittin-induced increase of paw thickness (edema). These experimental findings suggest that COX-1 plays an important role in the melittin-induced nociceptive responses.

• Biomolecules & Therapeutics
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• 제18권2호
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• pp.197-204
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• 2010

To establish the anti-inflammatory activity of the total flavonoid fraction of the root barks of Broussonetia papyrifera (EBP) and a new formula, the ethanol extract of the root barks of B. papyrifera was fractionated with ethylacetate, yielding the hydrophobic prenylated flavonoid-enriched fraction. EBP and the ethanol extract of the whole Lonicera japonica (ELJ) plant were then mixed at a ratio of 1:1 (w/w) to give a new preparation (BL) in the hope of obtaining an optimal formula with a higher anti-inflammatory activity. Evaluation of the effects of these preparations on A23187-treated rat basophilic leukemia (RBL-1) cells revealed that EBP potently inhibited 5-lipoxygenase (5-LOX), while ELJ showed weak inhibition. Additionally, the mixture (BL) clearly showed stronger inhibitory effects against 5-LOX than either preparation alone. These preparations also inhibited cyclooxygenase-2-catalyzed $PGE_2$ and inducible nitric oxide (NO) synthase-catalyzed NO production by lipopolysaccharide-treated RAW 264.7 cells. When tested against arachidonic acid-induced mouse ear edema, EBP showed strong inhibitory activity at doses of 5-200 mg/kg when administered orally, but BL had obviously stronger inhibitory effects. When tested against ${\lambda}$-carrageenan-induced paw edema in mice, BL showed a potent and synergistic anti-inflammatory effect. In addition, in the acetic acid-induced writhing test, BL was found to have strong analgesic activity at 50-400 mg/kg. Taken together, these results indicate that each of these preparations exert anti-inflammatory activity in vitro and in vivo. In particular, BL showed stronger anti-inflammatory activity than EBP, and these anti-inflammatory effects were partially related to the inhibition of eicosanoid and NO production. BL may be useful for the treatment of human inflammatory disorders.

• 한방안이비인후피부과학회지
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• 제20권2호통권33호
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• pp.10-35
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• 2007

Objectives : To investigate the effects of Ohbaesangami (OBSGM) on mucosa and skin diseases, anti-microbial and anti-inflammatory tests were performed using several in vitro test models. Results : In anti-microbial test, OBSGM showed the slight inhibitory effect against Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). In anti-oxidant test, OBSGM showed the potent radical scavenging activity. In anti-inflammatory test, OBSGM weakly inhibited the lipopolysaccharide (LPS)-induced nitric oxide(NO) release from the RAW 264.7 macrophage cells. OBSGM also inhibited the LPS-induced $interleukin-1{\beta}(IL-1{\beta})$ and cyclooxygenase-2 (COX-2) expressions. The inhibitory effects of OBSGM on macrophage activation was via the inhibition of $NF-{\kappa}B$, evidenced by transient transfection assay. Furthermore, OBSGM markedly inhibited the activation of Jun-N-terminal kinase (JNK) and p38 MAP kinase in RAW 264.7 cells. In skin wrinkle formation assay, OBSGM strongly inhibited collagnease and elastase, whose activities are tightly related with the wrinkle formation. In addition, OBSGM inhibited the activities of MMP-1, MMP-2 on the mRNA levels in RAW 264.7 cells. However, OBSGM did not show an inhibitory potential on tyrosinase activity and melanin synthesis, indicating that it could not be applicable for skin whitening. Conclusion : These results suggest that the anti-inflammatory effect of OBSGM may be due to its inhibitory potentials on the macrophage activation. And, the anti-wrinkle effects of OBSGM may be due to its inhibitory potential on the collagnease and elastase activities. Therefore, OBSGM could be applicable for the treatment of mucosa and skin diseases.

• Archives of Pharmacal Research
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• 제26권4호
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• pp.306-311
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• 2003

Soy, high dietary intake for the oriental population, is a main source of isoflavonoids. Sophoricoside (SOP) an isoflavone glycoside was isolated from immature fruits of Sophora japonica (Leguminosae family) and its inhibitory effect on chemical mediators involved in inflammatory response was investigated in this study. SOP inhibited the interleukin (IL)-6 bioactivity with an $IC_{50}$ value of 6.1 $\mu$M whereas it had no effects on IL-1$\beta$ and TNF-a bioactivities. SOP was identified as a selective inhibitor of cyclooxygenase (COX)-2 activity with an $IC_{50}$ value of 4.4 $\mu$ M, but did not show inhibitory effect on the synthesis of COX-2. However, SOP had no effect on the production of reactive oxygen species including superoxide anions and nitric oxide. These results revealed that in vitro anti-inflammatory action of SOP is significantly different from that of genistein known as a phytoestrogen of soy products. This experimental study has documented an importance of dietary soy isoflavonoids as multifunctional agents beneficial to human health, and will help to clarify protective mechanisms of SOP against inflammatory conditions.