• The Korean Journal of Pain
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• v.33 no.4
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• pp.335-343
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• 2020

Background: Zhongyi paste is a traditional Chinese medicine herbal paste that is externally applied to reduce inflammation and relieve pain. Methods: An acute foot swelling inflammation model in C57BL/6J mice was established by carrageenan-induced pathogenesis. Zhongyi paste raised the pain threshold and also reduced the degree of swelling in mice with carrageenan-induced foot swelling. Results: Analysis indicated that serum tumor necrosis factor-alpha, interleukin-1 beta, and prostaglandin E₂ (PGE₂) cytokine levels and PGE₂ levels in the paw tissue of the mice were decreased by Zhongyi paste treatment. The quantitative polymerase chain reaction and western blot results showed that Zhongyi paste downregulated the mRNA and protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2), and cyclooxygenase-2 (COX-2), and also downregulated the mRNA expression of PGE₂. At the same time, the Zhongyi paste exerted a stronger effect as an external drug than that of indomethacin, which is an oral drug, and voltaren, which is an externally applied drug. Conclusions: Our results indicated that Zhongyi paste is a very effective drug to reduce inflammatory swelling of the foot, and its mechanism of action is related to regulation of the ERK1/2-COX-2-PGE₂ 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 Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.961-966
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• 2007

Lesser yang person-Hyungbangpaedok-san (HBPDS) is a prescription originated in the

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.1051-1056
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• 2006

Rehmanniae radix preparata is the root of Rehmanniae glutinosa Liboschitz var. purpurea Makino which has been classified into Scrophulariaceae. Rehmanniae radix preparata has been used for the treatment of diabetes, for the relief of the pain, and for the anti-oxidative action. In this study, the effect of the aqueous extract of Rehmanniae radix preparata on lipopolysaccharide-induced inflammation was investigated by using 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), Western blot, prostaglandin E2 immunoassay, and nitric oxide (NO) detection in mouse BV2 microglial cells. In the present results, the aqueous extract of Rehmanniae radix preparata suppressed prostaglandin E2 (PGE2) synthesis and nitric oxide production by inhibiting the lipopolysaccharide-stimulated expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA and protein in mouse BV2 cells. These results show that Rehmanniae radix preparata exerts anti-inflammatory effect probably by suppressing of COX-2 and iNOS expressions.

• Journal of Ginseng Research
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• v.13 no.2
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• pp.202-210
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• 1989

The effects of Ginseng saponins on the in vitro biosynthesis of prostaglandins were examined in order to identify the role of some Ginseng components on the regulation of arachidonic arid metabolism. The productions of prostaglandin $E_2$ (PG$E_2$), $F_2$ (PGF2), thromboxane $B_2$(TX$B_2$) and 6-ketoprostaglandin Fl (6-Keto-PGF1) from [3Hl-arachidonic acid were evaluatpf by radiochromatographic analysis with rabbit kidney microtome, human platelet homogenate and bovine aortic microsome. The amounts of the total prostaglandins produced by cyclooxygenase activity and malondialdehyde from arachidonic acid didn't show significant changes in the presence of Ginseng saponins. Both of panaxadiol and panaxatriol didn't affect the production of PG$E_2$ while the formations of PG$F_2$( and TX$B_2$( were nearkedly reduced and the production of prostacyclin was increased. The formation of TXBE was reduced by ginsenoside $Rb_2$, Rc, and Re, however the production of 6-Keto-PGF1 was increased dose dependently up to 1 mg/ml. Moreover, platelet aggregations induced by arachidonic acid and U46619 (9.11-methanepoxy PG$H_2$), TX$A_2$ mimetics, were also inhibited by three ginsenosides. The effect of G-Re on prostacyclin synthetase was inhibited by tranylcypromine, prostacyclin synthetase inhibitor. These results suggest that Ginseng saponins may not directly act on cyclooxygenase but affect on the divergent pathway from endoperoxide.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.169-177
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• 2004

Background : Cyclooxygenase is the main target enzyme for the nonsteroidal anti inflammatory drugs (NSAIDs) that have been shown to suppress carcinogenesis in both experimental models and epidemiological studies. COX-2 plays an important role in solid tumor growth, invasiveness and angiogenesis, through, in part, the synthesis of prostaglandins, such as prostaglandin E2 (PGE2). In this study, the prognostic significance of an increase in COX-2 expression in lung cancer samples was evaluated. Material and Methods : The expression of COX-2, by immunohistochemistry, was studied in paraffin-embedded tumor blocks obtained from 84 patients(male 67, female 17, with a mean age of 63, ranging from 34 to 84 years) who had undergone surgery at Wonkwang University Hospital, between 1997 and 2002. For the evaluation of the relationships between COX-2 expression, and the clinical stage, metastasis to lymph nodes and survival, those cases showing the respective antigen expression in >10% of the tumor cells were considered positive. Result : Of the 84 patients, 61 (73%) exhibited more than 10% COX-2 immunoreactivities in the tumor and normal cells, whereas the remaining 23 showed no increase in the expression of COX-2. There was no significant relationship between the increased expression of COX-2 and the disease stage(p=0.1002) or cell type(p=0.152). The median survival was longer for the patients with a negative, compared to positive, COX-2 expression(36 compared to 24 months, p<0.05). The two year-survival rate was also higher in the patients with a negative COX-2 expression (78%) than those with a positive expression (47%, Kaplan-Meier, Log Rank, p < 0.05). Conclusion : The median survival was longer in the patients with a negative, compared to positive, COX-2 expression was longer than those with positive COX-2, having undergone complete resection due to primary non-small cell lung cancer.

• Biomedical Science Letters
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• v.21 no.2
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• pp.115-121
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• 2015

Ulcerative colitis (UC) is an inflammatory bowel disease, which is a chronic gastrointestinal disorder. Pulsatilla koreana (P. koreana) is a perennial plant that grows around Korea and it has various pharmacological effects such as anti-cancer and anti-inflammatory activity. However, the regulatory effects of P. koreana in intestinal inflammation are not yet understood. This study attempted to determine the effect of P. koreana in dextran sulfate sodium (DSS)-induced colitis in mice. The colitis mice were induced by drinking water containing 5% DSS for 7 days. The results showed that mice treated with DSS showed remarkable clinical signs, including weight loss, and reduced colon length. Administration of P. koreana attenuated DSS-induced the weight loss, colon shortening and Disease activity index in mice. Additionally, P. koreana inhibited the cyclooxygenase-2 and prostaglandin $E_2$ levels in DSS-treated colon tissues. These results provide experimental evidence that P. koreana might be a useful therapeutic medicine for patients with UC.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.70.1-70.1
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• 2003

Celecoxib, the selective cyclooxygenase-2 (COX-2) inhibitor, has recently been reported to reduce the formation of polyps in patients with familial adenomatous polyposis. This specific COX-2 inhibitor also protects against experimentally induced carcinogenesis, but molecular mechanisms underlying its chemopreventive activities remain largely unresolved. In the present work, we found that celecoxib inhibited 12-O- tetradecanoylphorbol-13-acetate (TPA)-induced expression of COX-2 in female ICR mouse skin when applied topically 30 min prior to TPA as determined by both immunoblot and immunohistochemical analyses. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.122.2-122.2
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• 2003

Gelatin protein is derived from animal collagen tissues and is therefore present in many kinds of animal protein food. The biological origin and biocompatibility of gelatin has led to wide-ranging applications in the pharmaceutical and medical fields; for example, as sealants for vascular prostheses, bone-repairing materials, wound healing agents and scaffolds for tissue engineering purposes. In the present study, we investigated the effects of collagen and gleatin on the cyclooxygenase-2 (COX-2) gene which plays a crucial role in many physiological and pathological processes in macrophages. (omitted)

• Journal of Life Science
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• v.19 no.10
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• pp.1396-1402
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• 2009

Hizikia fusiforme is a kind of edible brown seaweed that grows mainly in the northwest Pacific including Korea, Japan and China, and has been widely used as food in Korea. Induction of cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In this study, we investigated the effects of extracts of H. fusiforme on the expression of COX-2 and production of $PGE_2$ in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate 13-acetate (PMA) to mimic inflammation, methanol extract of H. fusiforme (MEHF) and ethanol extract of H. fusiforme (EEHF), but not water extract of H. fusiforme (WEHF), inhibited PMA-induced expression of both COX-2 protein and mRNA, which was associated with inhibition of $PGE_2$ production. To investigate the mechanism by which MEHF and EEHF inhibit COX-2 gene expression and $PGE_2$ production, we examined the activation of nuclear factor-kappaB (NF-$\kappa$B) in U937 cells. Pre-treatment with MEHF and EEHF significantly attenuated the PMA-induced IkappaB degradation and prevented nuclear translocation of NF-$\kappa$B. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-inflammatory activity of H. fusiforme.