• YAKHAK HOEJI
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• v.49 no.1
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• pp.103-108
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• 2005

Tacrine analogues for degenerative brain disease treatments have been designed. A series of diazaanthrine derivatives as novel analogues of tacrine has been prepared through the alkyl substitution and the ring expansion. They were expected to retain anti-inflammatory activity by inhibition of prostaglandin production with reduction of side effect as the selective prostaglandin synthase inhibitor. Prostaglandin synthase expression is associated with the deposition of beta-amyloid protein in neuritic plaques in brain inflammation. Therefore selective prostaglandin synthase blockade is important for the prevention and treatment of alzheimer's disease. To evaluate inhibitory effect of prostaglandin synthase, synthetic tacrine derivatives were screened with accumulation of prostaglandin biosynthesis by lipopolysaccharide in aspirin-treated murine macrophage cell. Most of synthetic compounds have shown significant prostaglandin synthase activities in vitro screening with $84.3{\sim}33.6\%$ inhibition of the prostaglandin $E_2$ production at $10\;{\mu}g/ml$.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.455-459
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• 2006

The inhibitors of prostaglandin $E_2\;(PGE_2)$ production and cyclooxygenase-2 (COX-2) activity have been considered as potential anti-inflammatory agents. In this study, we evaluated 9 compounds isolated from 5 Korean phytomedicinal plants (Spirea prunifolia, Paeonia suffruticosa, Salvia miltiorrhiza, Scutellaria baicalensis, and Artemisia capillaris) for the inhibition of $PGE_2$production and COX-2 expession in lipopolysaccharide (LPS)-stimulated human macrophages U937 cells. As a result, several compound such as prunioside A, penta-O-galloyl-beta-D-glucose, tanshinone IIA, baicalin, baicalein, wogonin, scopolatin, scoparone and decursinol showed potent inhibition of $PGE_2$production (50-70% inhibition at the test concentration of $10\;{\mu}M$). In addition, these compounds were also considered as potential inhibitors of COX-2 activity (45-73% inhibition at the test concentration of $10\;{\mu}M$). These active compound mediating COX-2 inhibitory activities are warranted for further elucidation of active principles for development of anti-inflammatory agents and these properties may contribute to the anti-atopic dermatitis activity.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.272-278
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• 2000

The antiinflammatory mechanism of NSAIDs is attributed to the reduction of prostaglandin synthesis by the direct inhibition of cyclooxygenase. Inhibition of prostaglandin production in organs such as stomach and kidney can result in gastric lesions, nephrotoxicity and increased bleeding. In this study, newly designed COX-2 inhibitors, synthesized 1,2-benzothiazine derivatives, were screened in vitro for selectivity of COX-1 and COX-2 inhibition properties. Lead compounds in the structure-activity relationship were studied to synthesize new highly selective COX-2 inhibitors.13 determine inhibitory effect of COX-2, synthesized 1,2-benzothiazine derivatives were screened with accumulation of prostaglandin by lipopolysaccharide (LPS) in aspirin-treated macrophages and murine macropharge cell. Some of synthesized 1,2-benzothiazine derivatives were shown to be effective as selective COX-2 inhibitory activity. Others exhibited a preferential inhibition of COX-2, although some COX-1 inhibitory activity was still present. As a conclusion, simple monomer derivatives were more active than dimer derivatives. Substitution of halogen (Br, C1) on the benzothiazine nucleus slightly enhanced inhibition activity.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.288-297
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• 2009

Objective : Inflammatory cytokines have a close relationship to insulin dependent diabetes mellitus (IDDM). The inhibitory effect of Smilacis Glabrae Rhizoma (SGR) were examined on production of nitric oxide (NO), prostaglandin $E_2$ $(PGE_2)$, synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and NF-${\kappa}$B activation in Raw 264.7 cells. Methods: Raw 264.7 cells were pretreated with SGR(20, 50, 100 ${\mu}g$/ml), and then cultured with lipopolysaccharides (LPS). Cell viability was measured by MTT assay; inhibition of NO, $PGE_2$, and TNF-${\alpha}$ production were measured by Griess reagent and enzyme-linked immunosorbent assay(ELISA). Induction of COX-2 and iNOS were determined by western blotting analysis. Inhibition of NF-${\kappa}$B was measured by immunofluorescence assay (IFA). Results: SGR inactivated NF-${\kappa}$B, and inhibited the production of NO, iNOS, and $PGE_2$. Inhibition of COX-2 and TNF-${\alpha}$ could not be confirmed. Conclusions: From the above result. SGR was found to have an anti-inflammatory effect of inhibition of NO, iNOS, and $PGE_2$ production via inhibition of NF-${\kappa}$B.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.188-193
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• 2001

Free radical scavengers or quenching agents for reactive oxygen species (ROS) present in consumable fruits, vegetables, and beverages have received considerable attention as potential antioxidants, and thus uses for treatment of several human diseases. In this study, grapevine shoot extract (GSE) containing high concentration of resveratrol and viniferine was evaluated for antioxidant potential and inhibition of pro-inflam-matory mediator production. Utilizing 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity and xanthine oxidase (XOD) inhibition assay the GSE showed inhibitory effects of DPPH radical scavenging and XOD activity with the $IC_{50}$/ values of 34.5 and 155 $\mu\textrm{g}$/ml, respectively. In addition, GSE also exhibited the inhibition of prostaglandin E$_2$ (PGE$_2$) and nitric oxide (NO) production in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 cells with the $IC_{50}$/ value of 6.4 and 14.5 $\mu\textrm{g}$/ml, respectively. This result suggests that grapevine shoot extract has the potential activity as a natural antioxidant or antiinflammatory agent.

• Biomolecules & Therapeutics
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• v.16 no.2
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1295-1302
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• 2006

Our preliminary aim is to elucidate the pharmacokinetic features of the PNS(Panax notoginseng Buck F.H. Chen. (Arialiaceae) root). First, we assessed the prevention of neurtrophil functions. A Panax notoginseng inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B4 production, without any effect on 5-lipoxygenase activity. This Panax notoginseng reduced nitric oxide (NO) and prostaglandin E2 production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. Panax notoginseng significantly reduced mouse paw oedema induced by carrageenan. The results indicate that Panax notoginseng exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E2 production, which could be due to a decreased expression of inducible NO synthase and cyclo-oxygenase-2.

• YAKHAK HOEJI
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• v.42 no.6
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• pp.558-566
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• 1998

Two isoforms of cyclooxygenase (COX) have been identified - COX-1, which is constitlitively expressed in most tissues, and the inducible form, COX-2, of which expression is induced by inflammatory signals and mitogens. It has been considered that the beneficial effects of NSAIDs are due to the inhibition of COX-2 activity and the side effects are from the inhibition of COX-1 activity. Therefore, it is essential to develop selective COX-2 inhibitor for developing new GI-tolerable NSAIDS. To discover new leads for developing selective COX-2 inhibitors, three-hundred extracts of natural products were primarily screened with the system of prostaglandin accumulation in LPS-stimulated mouse peritoneal macrophages. To identify whether these inhibitory activities of crude extracts on the accumulation of Prostaglandins were derived from direct action against COX-2, the effects of selected extracts on exogenous arachidonic acid-derived production of prostaglandins by LPS-stimulated macrophages were determined. Among them, 5 methanol extracts of natural products, such as Zingiberis Rhizoma, Alpinae Officinarum Rhizoma, Caryophilli Flos, Scutellariae Radix, Dalbergia ordorifera. inhibited more than 70% of the prostaglandin production in LPS-stimulated mouse peritoneal macrophages at a con-centration of 1${\mu}$g/ml.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.246.1-246.1
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• 2001