• The Journal of Korean Medicine
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• v.25 no.3
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• pp.90-98
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• 2004

Objectives : The present study was undertaken to investigate the molecular mechanisms of Ichungwhan for inhibition of cyclooxygenase-2 (COX-2) gene expression via suppression of NF-κB (nuclear factor κB) using aged rats. NF-κB is the most important modulator of inflammation and NF-κB regulates the gene expression of several pro-inflammatory cytokines, such as COX-2. Methods : In the experiment, we investigated the scavenging property of Ichungwhan on reactive species (RS) including nitrogen-derived species (RNS), measured by DCF-DA (2,7-dichlorodihydrofluorexcein diacetate) / DHR 123 (dihydrorhodamine 123) assay. Protein expression levels of COX-2, NF-κB, p-ERK and p-p38 were assayed by western blot. Results : We showed that Ichungwhan inhibits RS including RNS and inhibits NF-κB activation by blocking the dissociation of inhibitory IκB-β via suppression of IKK pathway. Also, Ichungwhan inhibits COX-2 gene expression. Conclusions : These findings suggest that Ichungwhan modulates COX-2 gene expression via suppression of the NF-κB pathway.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.832-839
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• 2003

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and produce excessive amounts of nitric oxide (NO) and prostaglandin E$_2$ (PGE$_2$), which play key roles in the processes of inflammation and carcinogenesis. The root of Paeonia lactiflora Pall., and the root cortex of Paeonia suffruticosa Andr., are important Chinese crude drugs used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) is a major bioactive constituent of both crude drugs. PGG has been shown to possess potent anti-oxidant, anti-mutagenic, anti-proliferative and anti-invasive effects. In this study, we examined the inhibitory effects of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) isolated from the root of Paeonia lactiflora Pall. on the COX-2 and iNOS activity in LPS-activated Raw 264.7 cells, COX-1 in HEL cells. To investigate the structure-activity relationships of gallate and gallic acid for the inhibition of iNOS and COX-2 activity, we also examined (-)-epigallocatechin gallate (EGCG), gallic acid, and gallacetophenone. The results of the present study indicated that PGG, EGCG, and gallacetophenone treatment except gallic acid significantly inhibited LPS-induced NO production in LPS-activated macrophages. All of the four compounds significantly inhibited COX-2 activity in LPS-activated macrophages. Among the four compounds examined, PGG revealed the most potent in both iNOS ($IC_{50}$ = 18 $\mu\textrm{g}/mL$) and COX-2 inhibitory activity (PGE$_2$: $IC_{50}$ = 8 $\mu\textrm{g}/mL$ and PGD$_2$: $IC_{50}$ = 12 $\mu\textrm{g}/mL$), respectively. Although further studies are needed to elucidate the molecular mechanisms and structure-activity relationship by which PGG exerts its inhibitory actions, our results suggest that PGG might be a candidate for developing anti-inflammatory and cancer chemopreventive agents.

• Journal of Ginseng Research
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• v.38 no.1
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• pp.34-39
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• 2014

Cigarette smoke is considered a major risk factor for vascular diseases. There are many toxic compounds in cigarette smoke, including acrolein and other ${\alpha},{\beta}$-unsaturated aldehydes, which are regarded as mediators of inflammation and vascular dysfunction. Furthermore, recent studies have revealed that acrolein, an ${\alpha},{\beta}$-unsaturated aldehyde in cigarette smoke, induces inflammatory mediator expression, which is known to be related to vascular diseases. In this study, we investigated whether Korean Red Ginseng (KRG) water extract suppressed acrolein-induced cyclooxygenase (COX)-2 expression in human umbilical vein endothelial cells (HUVECs). Acrolein-induced COX-2 expression was accompanied by increased levels of phosphorylated p38 in HUVECs and KRG inhibited COX-2 expression in HUVECs. These results suggest that KRG suppresses acrolein-induced COX-2 expression via inhibition of the p38 mitogen-activated protein kinase signaling pathway. In addition, KRG exhibited an inhibitory effect on acrolein-induced apoptosis, as demonstrated by annexin Vepropidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Consistent with these results, KRG may exert a vasculoprotective effect through inhibition of COX-2 expression in acrolein-stimulated human endothelial cells.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.61-72
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• 2006

Objectives : Human chondrocytes co-treated with Buthus martensi Karsch herbal acupuncture solution(BMK-HAS) extract produced significantly less NO compared with chondrocytes stimulated with $IL-1{\beta}$ alone Methods : Activation and translocation of and NF-kB DNA binding activity were determined by Western blotting and specific enzyme-linked immunosorbent assay. Results : The inhibition of NO production correlated with the suppression of induction and expression of nuclear factor-kB (NF-kB) and activation protein-1 (AP-1)-dependent gene. BMK-HAS inhibited the activation and translocation of NF-kB to the nucleus, indicating that BMK-HAS inhibits the $IL-1{\beta}-induced$ production of NO in human chondrocytes by interfering with the activation of NF-kB through a novel mechanism. In addition, BMK-HAS reduced prostaglandin E2 (PGE2)production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2) or cyclooxygenase-1 (COX-1) was observed. My data, therefore, suggest that BMK-HAS may be a therapeutically effective inhibitor of $IL-1{\beta}-induced$ inflammatory effects that are dependent on NF-kB activation in human OA chondrocytes. Conclusion : The results indicate that BMK-HAS exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and PGE2 production, which could be due to a decreased expression of iNOS and COX-2 through the transcription factors NF-kB and AP-1.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.247-251
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• 2004

UV radiation exerts various influences in the skin, including photoaging and inflammation (1). The MMPs (Matrix metalloproteinases), which are induced by UV irradiation, can degrade matrix proteins, and these results in a collagen deficiency in photodamaged skin that leads to skin wrinkling. It has been known that the production of PGE$_2$ stimulates MMPs expression, and inhibits procollagen (2). Thus, it is possible that the induction of MMPs and the inhibition of matrix protein synthesis by UV -induced PGE$_2$ may play some role in UV-induced collagen deficiency in photoaged skin. Fructose-1,6-diphosphate (FDP), a glycolytic metabolite, is reported to have cytoprotective effects against ischemia and postischemic reperfusion injury of brain and heart, presumably by augmenting anaerobic carbohydrate metabolism (3). And also, FDP significantly prevent skin aging by decreasing facial winkle compared with vehicle alone after 6 months of use. We studied the mechanism of anti-aging effect of FDP on UVB-irradiated HaCaT keratinocyte model. FDP has protective role in UVB injured keratinocyte by attenuating prostaglandin E$_2$ (PGE$_2$) production and COX-2 expression. And FDP also suppressed UVB-induced MMP-2 expression. Further, to delineate the inhibition of UVB-induced COX-2 and MMPs expression with cell signaling pathways, treatment of FDP to HaCaT keratinocytes resulted in marked inhibition of UVB-induced phosphorylation of ERK1/2, JNK. It also prevents UV induced NFB translocation, which are activated by cellular inflammatory signal. Our results indicate that FDP has protecting effects in UV-injured skin aging by decreasing UVB-induced COX-2 and MMPs expression, which are possibly through blocking UVB-induced signal cascades.

• YAKHAK HOEJI
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• v.42 no.2
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• pp.214-219
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• 1998

Tissue distributions and association of cyclooxygenase-2 (COX-2) with inflammatory have led us to search for COX-2 selective inhibitors from natural products. Conceptually, COX- 2 selective inhibitors should be expected to retain anti-inflammatory efficacy by inhibition of PGs production while reducing or eliminating the gastric, renal and hemostatic side effects commonly associated with NSAIDs use. Thus, a logical approach to the treatment of inflammatory diseases should involve the inhibitors of COX-2. To develop new COX-2 inhibitors from natural products, two hundred crude drugs were screened by inhibiting PGD2 generation in bone marrow derived mast cells (BMMC). Among them, 6 methanol extracts of crude drugs such as, Bletillae rhizoma, Aconiti kgreani rhizoma, Belamcandae rhizoma, Nelumbinis semen, Gleniae radix, Aurantii immatri pericarpium inhibited more than 85% of BMMC COX-2 activity at a concentration 2.5${\mu}$g/ml.

• International Journal of Oral Biology
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• v.31 no.1
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• pp.21-26
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• 2006

Periodontopathogens including Porphyromonas gingivalis interact with host periodontal cells and the excessive subsequent host responses contribute a major part to the development of periodontal diseases. Cyclooxygenase(COX)-2-synthesized $PGE_2$ has detrimental activities in terms of periodontal pathogenesis. The present study investigated induction of COX-2 expression by P. gingivalis in human monocytic THP-1 cells. Live P. gingivalis increased expression of COX-2, but not that of COX-1, which was demonstrated at both mRNA and protein levels. Elevated levels of $PGE_2$ were released from P. gingivalis-infected THP-1 cells. Pharma-cological inhibition of p38 mitogen-activated protein kinase(MAPK) and extracellular signal-regulated kinase(ERK) substantially attenuated P. gingivalis-induced COX-2 mRNA expression. Indeed, activation of p38 MAPK and ERK was observed in P. gingivalis-infected THP-1 cells. Also, P. gingivalis induced activation of nuclear $factor-{\kappa}B\;(NF-{\kappa}B)$ which is an important transcription factor for COX-2. These results suggest that COX-2 expression is up regulated in P. gingivalis-infected monocytic cells, at least in part, via p38 MAPK, ERK, and $NF-{\kappa}B$.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.329-335
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• 2002

Previously, several prenylated flavonoids having a C-8 lavandulyl moiety were found to inhibit cyclooxygenase-1 (COX-1) as well as 5-lipoxygenase (5-LOX), and sophoraflavanone G was the most potent inhibitor against these eicosanoid generating enzymes among 19 prenylated flavonoids tested. In this investigation, effects of sophoraflavanone G on COX-2 induction from RAW 264.7 cells and in vivo inflammatory response were studied. Sophoraflavanone G inhibited prostaglandin $E_2{\;}(PGE_2)$ production from lipopolysaccharide (LPS)-treated RAW cells by COX-2 down-regulation at 1-50 uM. Other prenylated flavonoids including kuraridin and sanggenon D also down-regulated COX-2 induction at 10-25 uM, while kurarinone and echinoisoflavanone did not. In addition, sophoraflavanone G showed in vivo anti-inflammatory activity against mouse croton oil-induced ear edema and rat carrageenan paw edema via oral (2-250 mg/kg) or topical administration (10-250 ug/ear). Although the potencies of inhibition were far less than that of a reference drug, prednisolone, this compound showed higher anti-inflammatory activity when applied topically, suggesting a potential use for several eicosanoidrelated skin inflammation such as atopic dermatitis.

• The Journal of Korean Medicine
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• v.29 no.5
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• pp.111-117
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• 2008

Objectives and methods : Previous mechanistic studies suggest the cyclooxygenase-2 (COX-2) inhibitors represent the good candidates against tumor progression. MeOH extract of the stem barks of Euonymus alatus induced the strong inhibition of COX-2. A phenolic compound responsible for the anti- COX-2 known to involve in tumor adhesion and invasion has been studied through the methanol extracts. The compound, rosmarinic acid (ROS-A) was an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. ROS-A showed a strong inhibitory effect of COX-2 activity in a concentration-dependent manner. Then we have measured the IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production related the immune regulation, induction of inflammatory related genes. Results and Conclusions :Hep3B cells produce proinflammatory cytokines of IL-1${\beta}$, IL-6 and TNF-${\alpha}$ while ROS A inhibited the cytokines production. Since IL-1${\beta}$, IL-6 and TNF-${\alpha}$ need the transcription factors such as nuclear factor- ${\kappa}$B (NF-${\kappa}$B) and activated protein-1 (AP-1), we measured the transcription factors. ROS-A inhibited the activation of p65, p50, c-Rel subunits of NF-${\kappa}$B and AP-1 transcription factors. These findings indicate that ROS A from the stem bark of E. alatus inhibits proliferation in metastatic cancer cells. It was suggested that stem barks of E. alatus could be suitable for anti-cancer drugs.

• 대한두경부종양학회:학술대회논문집
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• 2001.05a
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• pp.72-72
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• 2001