• 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 $PGE_2$.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.4
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• pp.215-221
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• 2005

We investigated the effects of testosterone and dihydrotestosterone on inflammatory response of iNOS and COX-2 expression in rat vascular smooth muscle cells. Rat vascular smooth muscle cells (VSMC) stimulated with bacterial lipopolysaccharide $(LPS;\;10{\mu}g/ml)$ for 24 hours were incubated with increasing amounts of testosterone and dihydrotestosterone (1 and 100 nM). LPS was found to induce inflammatory response of iNOS and COX-2 mRNA and protein in VSMC. These processes were affected by male sex steroid hormones. For 3 hours, however, pretreatment of the cells with 100 nM each of testosterone and dihydrotestosterone suppressed LPS induced iNOS and COX-2 protein expression. RT-PCR analysis revealed that testosterone and dihydrotestosterone did not inhibit mRNA expression of iNOS and COX-2 stimulated by 24 hours of LPS incubation. Proliferation rate was slower in VSMC treated with testosterone and dihydrotestosterone. Testosterone enhanced androgen receptor expression, and LPS significantly reduced androgen receptor protein expression in VSMC. These results indicate that the expression of both iNOS and COX-2 proteins was suppressed by testosterone and dihydrotestosterone in LPS stimulated VSMC and leading to reduction of vascular inflammation.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.246-252
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• 2014

Background: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. Methods: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. Results: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). Conclusions: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.

• Journal of Life Science
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• v.21 no.12
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• pp.1689-1697
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• 2011

In this study, we investigated the anti-inflammation effect of Persicaria thunbergii (P. thunbergii) on RAW 264.7 murine macrophage cells. The anti-inflammatory activity of P. thunbergii was determined by measuring expression of the LPS-induced inflammatory proteins, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and the production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). Methanol extract of P. thunbergii decreased the expression of iNOS, COX-2 and NF-${\kappa}B$, and increased the expression of HO-1 in LPS-stimulated RAW264.7 cells. Methanol extract was fractioned by n-butanol, hexane and ethyl acetate (EtOAc) and each fraction was tested for inhibitory effects on inflammation. Among the sequential solvent fractions, the EtOAc soluble fraction was investigated by the expression of prostaglandin $E_2$ ($PGE_2$), and showed decreasing form to the dose-dependent manner. EtOAc extract showed the most effective inhibitory activity of the expression of iNOS, COX-2 and NF-${\kappa}B$, and the production of NO. The study showed that P. thunbergii has anti-inflammatory activity through the decrease of NO and inhibition of iNOS, COX-2, $PGE_2$ and NF-${\kappa}B$ expression, and by the increase of HO-1 enzyme. This study needs for more investigation to find out the most effective single compound with anti-inflammatory activity.

• The Journal of Korean Medicine
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• v.25 no.3
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• pp.1-11
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• 2004

Objectives : This study was carried out to investigate the effect of Samooltang (SMT) on the injury of gastric mucous membrane by ethanol in mice. Methods : The normal group was mice with no inflammation. The control group was mice with gastro-inflammation elicited by ethanol. The sample group was SMT-administered mice before gastro-inflammation elicitation. Results : In the immunohistochemical change, the distribution of SBA and COX-1 treated with SMT noticeably increased over the control group (p<0.05). The distribution of NF-κB P50, COX-2, and TUNEL treated with SMT noticeably decreased over the control group (p<0.05). The distribution of SMT was the same as the normal group. Conclusions : According to the above results, it is supposed that SMT would be helpful against gastritis and gastric ulcer caused by alcoholic drinks.

• The Journal of Korean Medicine
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• v.23 no.4
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• pp.32-44
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• 2002

Objective: In this study, we investigated the effects of Rhizoma Cimicifugae (RC) on the induction of nitric oxide (NO) in RAW 264.7 murine macrophages treated with lipopolysaccharide (LPS). Methods: We examined whether RC have an antipyretic effect by inhibition of COX and/or NOS in fever that is evoked by an intraperitoneal injection of LPS in rats. Results: 1. RC inhibited NO metabolites produced by activated murine macrophage in a dose-dependent manner. 2. RC had an antipyretic effect in a dose-dependent manner in LPS-induced fever. 3. RC inhibited levels of both COX-2 protein and iNOS protein increased by the treatment of LPS in brain tissues as well as brain blood vessels. 4. There were no changes in proteins of nNOS/COX-1. Conclusions: RC has an antipyretic effect by attenuating the level of iNOS and COX-2 protein.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.250.2-250.2
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• 2003

A series of rutaecarpine homologues were prepared from 2,3-polymethylene-4(3H-quinazolinones in 4 steps [i) PhCHO/Ac$_2$O, ⅱ) O,$_3$ ⅲ) PhNHNH$_2$HCl, and ⅳ) PPA], in which dihedral angles of the two planar aromatic rings (indole and 4(3H)-quinazolinone) were controlled in a regular fashion. Their inhibitory activities on COX-1 and COX-2 were evaluated to show that the inhibitory activities were increased with the increase of the length of methylene unit while selectivities on COX-2 decreased leading a loss in trimethylene bridged system.

• Journal of Nutrition and Health
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• v.38 no.1
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• pp.30-39
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• 2005

The effects of different concentrations of estrogen supplementation to mature female rats or estrogen supplementation to ovariectomized rats on cyclooxygenase-2 (COX-2) expression, PGE$_2$ production and mapkinases expression were investigated in experimentally induced atherogenic rats with feeding a high fat. high cholesterol diet. In the first experiment using 48-week old mature rats, the supplementation of three different levels of estrogen was compared to the basal diet. The high concentration of estrogen supplementation induced the marked up-regulation of COX-2 protein and the increase in plasma PGE$_2$ production and this seems to be followed by the up-regulation of p38 among mapkinases. The regulation of bax showed in a reverse trend of COX-2 in heart tissues of mature female rats. In the second ex-perimental system, female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were supplied with basal diet to sham-operated control group and ovariectomized control group, and estrogen supplemented diet to ovariectomized group for an eight-week experimental period. In a group supplemented with a medium dose of estrogen, COX-2 expression was up-regulated. This up-regulation was accompanied by the elevated expression of pERK1/2. Bax was increased in estrogen-fed animals indicating bax might be involved in estrogen feeding state in ovariectomized rats. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by estrogen are required in in vivo system of female rats at the various physiological states.

• Korean Journal of Pharmacognosy
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• v.41 no.1
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• pp.14-20
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• 2010

In this study, we investigated the anti-inflammatory effects of fupenjic acid (FA) isolated from the Potentilla discolor in both RAW 264.7 and mouse primary peritoneal macrophage cells. FA pretreatment significantly inhibited nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ productions in the lipopolysaccharide (LPS)-induced RAW 264.7 and mouse primary peritoneal macrophage cells. Consistent with these observations, Western blot and RT-PCR analyses revealed that FA inhibited the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels. In addition, FA reduced the release of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6). These results suggest that the down regulation of iNOS and COX-2 expression and TNF-$\alpha$ and IL-6 production by fupenjic acid are responsible for its anti-inflammatory effects.

• Korean Journal of Oriental Medicine
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• v.8 no.1
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• pp.65-74
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• 2002

Inflammation is a disease that continues to afflict large numbers of people and may cause other diseases, for example, rheumatoid arthritis, colon cancer, etc. prostaglandins(PGs), one of arachidonic acid metabolites, are major chemical mediators in the process of inflammation. In traditional herbal medicine, many kinds of herbal drugs have been widely used for the treatment of inflammation. So, we analyzed many publications until 2001 which worked on inhibition of $PGE_2$ synthesis by cyclooxygenase-2 (COX-2) with herbs and herb oriented single compounds. And then we tried to make interpretations of herbal traditional prescriptions for inflammation. There are significant correlations between herbal medicine prescribed and inhibitions of COX-2 activity. From our efforts and further researches, we expect to develop new-inflammatory herbal drugs which have more efficacy and fewer side effects.