• BMB Reports
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• v.42 no.9
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• pp.552-560
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• 2009

Cyclooxygenases (COX-1 and COX-2) are ER-resident proteins that catalyze the committed step in prostanoid synthesis. COX-1 is constitutively expressed in many mammalian cells, whereas COX-2 is usually expressed inducibly and transiently. Abnormal expression of COX-2 has been implicated in the pathogenesis of chronic inflammation and various cancers; therefore, it is subject to tight and complex regulation. Differences in regulation of the COX enzymes at the posttranscriptional and posttranslational levels also contribute significantly to their distinct patterns of expression. Rapid degradation of COX-2 mRNA has been attributed to AU-rich elements (AREs) at its 3’UTR. Recently, microRNAs that can selectively repress COX-2 protein synthesis have been identified. The mature forms of these COX proteins are very similar in structure except that COX-2 has a unique 19-amino acid (19-aa) segment located near the C-terminus. This C-terminal 19-aa cassette plays an important role in mediation of the entry of COX-2 into the ER-associated degradation (ERAD) system, which transports ER proteins to the cytoplasm for degradation by the 26S proteasome. A second pathway for COX-2 protein degradation is initiated after the enzyme undergoes suicide inactivation following cyclooxygenase catalysis. Here, we discuss these molecular determinants of COX-2 expression in detail.

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.166-176
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• 2003

Objective : The aim of this study is to investigate the anti-inflammatory effects of 15Hz electroacupuncture(EA) on carrageenan-injected rats. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw. Methods : Bilateral EA stimulation with 15 Hz were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles for a total of 30 min duration in carrageenan-injected rats. Results: The developing edema was measured 30 minutes interval afer carrageenan injection and 15 Hz EA stimulation presented significant edema inhibition. Three hours after carrageenan injection, prostaglandin $E_2(PGE_2)$ and nitric oxide(NO) levels were measured. The 15Hz EA stimulation significantly inhibited $PGE_2$ and NO production in the right paw. The pro-inflammatory mRNA expression such as cyclooxygenases(COX)-2 and interleukin(IL)-$1{\beta}$ were slightly down-regulated by EA stimulation. The number of COX-2, IL-$1{\beta}$, tumor necrosis factor-${\alpha}$ immunoreactive cells were abundantly observed in paw edema. But these cells were decreased in nmber according to anti-edema effect of 15Hz EA. Conclusions: These results indicate that 15Hz EA stimulation have an alleviation action against carrageenan-induced edema and local inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.88-92
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• 2006

Genistein was tested for chemopreventive potential against breast cancer by measuring the effect on proliferation of human breast cancer cells, human placental aromatase activity and cyclooxygenases-2 (COX-2) expression and activity, Genistein inhibited the growth of estrogen-independent MDA-MB-231 human breast cancer cell. However, there is no inhibitory effect of genistein on human placental aromatase activity. The expression of COX-2 was inhibited by genistein in Western blot analysis. Genistein significantly inhibited COX-2 activity at the concentrations of 10 (p<0.05), 25 (p<0.05) and 50 ${\mu}M$ (p<0.01). These results suggest that genistein may have breast cancer chemopreventive potential by inhibiting the growth of human breast cancer cell and expression and activity of COX-2.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.16-23
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• 2010

Adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) is not as efficient as that in murine pre-adipocytes when induced by adipogenic agents including insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IDX condition). Therefore, the promotion of adipocyte differentiation in hBM-MSCs has been used as a cell culture model to evaluate insulin sensitivity for anti-diabetic drugs. In hBM-MSCs, $PPAR{\gamma}$ agonists or sulfonylurea anti-diabetic drugs have been added to IDX conditions to promote adipocyte differentiation. Here we show that troglitazone, a peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) agonist, significantly reduced the levels of anti-adipogenic $PGE_2$ in IDX-conditioned hBM-MSC culture supernatants when compared to $PGE_2$ levels in the absence of $PPAR{\gamma}$ agonist. However, there was no difference in the mRNA levels of cyclooxygenases (COXs) and the activities of COXs and prostaglandin synthases during adipocyte differentiation in hBM-MSCs with or without troglitazone. In hBM-MSCs, troglitazone significantly increased the mRNA level of 15-hydroxyprostaglandin dehydrogenase (HPGD) which can act to decrease $PGE_2$ levels in culture. These results suggest that the role of $PPAR{\gamma}$ activation in promoting adipocyte differentiation in hBM-MSCs is to reduce anti-adipogenic $PGE_2$ levels through the up-regulation of HPGD expression.

• Archives of Pharmacal Research
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• v.29 no.4
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• pp.282-286
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• 2006

Ochnaflavone is a medicinal herbal product isolated from Lonicera japonica 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 $IC_{50}$ values of $0.6{\mu}M$. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the $PGD_2$ product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene $C_4 (LTC_4)$ in a dose dependent manner, with an $IC_{50}$ value of $6.56 {\mu}M$. These results demonstrate that ochnaflavone has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound strongly inhibited degranulation reaction in a dose dependent manner, with an $IC_{50}$ value of $3.01{\mu}M$. Therefore, this compound might provide a basis for novel anti-inflammatory drugs.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.28-33
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• 2005

Seven diterpenes, four polyacetylenes, a lipid glycerol, and two sterols were isolated from the methylene chloride fraction of the root of Aralia cordata. Their chemical structures were determined as (-)-pimara-8(14), 15-dien-19-oic acid (2), pimaric acid (3), (-)-kaur-16-en-19-oic acid (4), 17-hydroxy-ent-kaur-15-en-19-oic acid (9), $7{\alpha}$-hydroxy-(-)-pimara-8(14), 15-dien-19-oic acid (10), $16\alpha$, 17 -dihydroxy-(-)-kauran-19-oic acid (11), 16-hydroxy-17-isovaleroyloxy-ent-kauran-19­oic acid (12), falcarindiol (5), dehydrofalcarindiol (6), dehydrofalcarindiol-8-acetate (7), falcarin­diol-8-acetate (8), alpha-mono palmitin (13), stigmasterol (1), and daucosterol (14) by the spectral evidences. These compounds were tested with COX-1 and COX-2 inhibition assays. This study found that compounds 2, 4, 5, 6, 7, 8, and 10 inhibited COX-1 dependent conversion of the exogenous arachidonic acid to $PGE_2$ in a dose-dependent manner with $IC_{50}$ values of $134.2{\mu}M$, $121.6{\mu}M$, $170{\mu}M$, $50.4{\mu}M$, $11.7{\mu}M$, $99.6{\mu}M$, and $69.6{\mu}M$, respectively. But, most of these compounds weakly inhibited COX-2 dependent $PGE_2$ generation. Among them, only compound 4 showed relatively significant inhibitory activity $(IC_{50}\;:\;127.6{\mu}M)$.

• Journal of Life Science
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• v.18 no.1
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• pp.96-102
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• 2008

Piceatannol is a polyphenol that is found in abundant quantities in grapes and wine. Although recent experimental data revealed the anti-cancer potency of piceatannol, the molecular mechanisms underlying the antileukemic activity have not yet been studied in detail. In the present study, we investigated further possible mechanisms by which piceatannol exerts its anti-proliferative action in cultured human leukemia U937 cells. Exposure of U937 cells to piceatannol resulted in growth inhibition and induction of apoptosis as measured by MTT assay and flow cytometry analysis, which was associated with S phase arrest of the cell cycle. Piceatannol treatment markedly inhibited the activity of telomerase, and the levels of human telomerase reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1), main determinants of the telomerase enzymatic activity, were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. However, the levels of cyclooxygenases (COXs) expression and prostaglandin E2 (PGE2) release were not changed in piceatannol-treated U937 cells. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of piceatannol.

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.177-193
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• 2003

Objective : The present studies investigated the effects of 120Hz high frequency electroacupunctue(EA) on the stress-induced stomach dysfunction in relation to its effect on the level of stress hormone and gastric mucosal damages. The gastric mucosal injury was induced by cold-restraint stress and two acupoints corresponding to Zusanli and Sanyinjiao in man were used. Methods: Cold-restraint stress produced typical gastric lesions in all rats of the stressed groups, but he number of ulcers as well as the mean ulcer diameter were reduced by 120 Hz EA pre-treatment. The cold-restraint stress also induced an increase in catecholamine response involving epinephrine, norepinephrine and dopamine, but an slight decline were observed in EA pre-treated rats compared with cold-restrained rats. Results: The degranulation value of gastric mast cell was significantly higher in cold-restrained rats than in control ones. However, with the significant reduction of degranulation values of gastric mast cells in EA pre-treated rats compared with cold-restrained ones, $PGE_2$ content in the gastric mucosa of EA pre-treated rats was also different from that observed in cold-restrained rats. Cold-restraint stress induced an elevated mRNA expression of pro-inflammatory gene such as cyclooxygenases-2 and tumor necrosis factor(TNF)-${\alpha}$, but these expression were down-regulated in EA pre-treated rats. Immunohistochemecal analysis showed that while the inhibitory-${\kappa}B{\alpha}$ an TNF-${\alpha}$ immunoreaction in the surface epithelium of the stomach tended to increase, both reactions in the EA pre-treated rats showed similar pattern as observed in controls. Conclusions : These results suggest that 120 Hz EA may act as a therapeutical means for gastric mucosal damages through a activation of pituitary adrenal system. it could be concluded that 120 hz high frequency electroacupuncture affords a good protective potential against stress-induce gastrointestinal dysfunction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1019-1030
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• 2003

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the growth of human lung carcinoma A549 cells. Results obtained are as fellow; AEPG treatment resulted in the inhibition of the cell viability of A549 cells in a concentration-dependent manner. Upon treatment with AEPG, A549 cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that AEPG increased populations of apoptotic-sub G1 phase. Western blot and RT-PCR analyses indicated that the expressions of Bcl-2 was down-regulated but Bax was up-regulated in AEPG-treated A549 cells. AEPG-induced apoptotis of A549 cells was associated with rroteolytic cleavage and activation of caspase-3, release of cytochrome c from mitochondria into cytosol and down-regulation of Akt and phospho-Akt proteins in a dose-dependent manner. Induction of apoptosis by AEPG treatment was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ 1. AEPG treatment inhibited the levels of cyclooxygenases protein of A549 cells, which was associated with the inhibition of prostaglandin E2 accumulation in a concentration-dependent fashion. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

• Korean Journal of Acupuncture
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• v.21 no.4
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• pp.101-115
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• 2004

Objective : The present studies investigated the effects of 120 Hz high frequency electroacupuncture (EA) on the stress-induced stomach dysfunction in relation to its effect on the level of stress hormones and gastric mucosal damages. The gastric mucosal injury was induced by cold-restraint stress and two acupoints corresponding to Zusanli and Sanyinjiao in man were used. Methods : Cold-restraint stress produced typical gastric lesions in all rats of the stressed groups, but the number of ulcers as well as the mean ulcer diameter were reduced by 120 Hz EA pre-treatment. Results : The degranulation value of gastric mast cell was significantly higher in cold-restrained rats than in control ones. However, with the significant reduction of degranulation values of gastric mast cells in EA pre-treated rats compared with cold-restrained rats. Cold-restarint stress induced an elevated mRNA expression of pro-inflammatory gene such as cyclooxygenases-2 and tumor necrosis factor $(TNF)-{\alpha}$, but these expression were down-regulated in EA pre-treated rats. Immunohistochemical analysis showed that while the $inhibitory-{\kappa}B{\alpha}$ and $TNF-{\alpha}$ immunorection in the surface epithelium of the stomach tended to increase, both reactions in the EA pre-treated rats showed similar pattern as observed in controls. Conclusion : These results suggest that 120 Hz EA may act as a therapeutical means for gastric mucosal damages through an activation of pituitary adrenal system. It could be concluded that 120 Hz high frequency electroaucupuncture affords a good protective potential against stress-induced gastrointestinal dysfunction.