• Title/Summary/Keyword: cyclo-oxygenase-2

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ARACHIDONIC ACID METABOLISM IN HYPERSENSITIVE HUMAN DENTAL PULP (지각과민성(知覺過敏性) 치아(齒牙) 치수조직(齒髓組織)의 Arachidonic Acid Metabolism에 관(關)한 연구(硏究))

  • Lee, Kyung-Hee;Son, Ho-Hyun
    • Restorative Dentistry and Endodontics
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    • v.15 no.1
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    • pp.153-164
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    • 1990
  • Human dental pulps obtained from normal teeth, hypersensitive teeth and teeth with inflamed pulp were studied to measure and to compare the endogenous levels of arachidonic acid metabolites in order to see the relative activities of the different pathways involved in arachidonic acid metabolism. Pulp homogenates were incubated with $^{14}C$-arachidonic acid and lipid solvent extracts were separated by thin layer chromatography (TLC) to be analyzed by autoradiography and TLC analyzer. 1. The most significant metabolite was HETEs showing $96.9{\pm}37.8$pmol/mg tissue protein/hr in normal pulp, $169.2{\pm}76.7$ in hypersensitive pulp and $385.4{\pm}113.2$ in inflamed pulp. In normal pulp $LTB_4$, 6-keto-$PGF_{1\alpha}+PGE_2$, $TXB_2$ and unidentified metabolite were formed in decreasing order. While in hypersensitive and inflamed pulp 6-keto-$PGF_{1\alpha}+PGE_2$, $LTB_4$, $TXB_2$ and unidentified metabolite were formed in decreasing order. 2. In hypersensitive pulp only HETEs were significantly increased when compared with that in normal pulp. The levels of all the converted metabolites in inflamed pulp were significantly increased compared with those in normal pulp. In inflamed pulp, the levels of $TXB_2$ and HETEs were significantly increased compared with those in hypersensitive pulp. 3. The ratio of each metabolites to the total converted metabolites showed an increased value of $TXB_2$ and 6-keto-$PGF_{1\alpha}+PGE_2$, as the degree of inflammation was increased, while that of HETEs decreased both in hypersensitive pulp and inflamed pulp more than in normal pulp. 4. The relative amounts of the total metabolites formed in lipoxygenase pathway to cyclo-oxygenase pathway were 6.8 fold in normal pulp, 4.4 fold in hypersensitive pulp and 3.8 fold in inflamed pulp.

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A COMPARATIVE STUDY ON THE ARACHIDONIC ACID METABOLITES IN HUMAN INFLAMMATORY DENTAL PULP AND PERIODONTAL TISSUES (사람의 염증성 치수와 치주조직에서 Arachidonic acid 대사산물에 대한 비교연구)

  • Son, Ho-Hyun;Kim, Hyung-Seop;Chang, Kee-Wan
    • Restorative Dentistry and Endodontics
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    • v.16 no.2
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    • pp.165-173
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    • 1991
  • The purpose of the present study was to measure and compare the arachidonic acid metabolites in diseased periodontal tissue and vital pulp tissue of the tooth, and to investigate the relationship between periodontal and pulp disease. Diseased periodontal tissue of periodontally involved human teeth and vital pulp tissue from the same teeth which were intact with no periapical lesions were obtained. Each periodontal and pulp tissue homogenates from the same tooth were incubated with $^{14}C$ - arachidonic acid. Lipid solvent extracts were separated by thin layer chromatography to be analyzed by autoradiography and TLC analyzer. 1. The conversion into $TXB_2$, 6 - keto - $PGF_{1a}$ and $PGE_2$, and unidentified metabolite in pulp tissue were less than that in diseased periodontal tissue(P<0.05). 2. Biosynthetic levels of $TXB_2$, unidentified metabolite, 6 - keto - $PGF_{1a}$ and HETEs were not satistically significant between diseased periodontal tissue and pulp tissue. $LTB_4$ was measured highly in pulp tissue(P<0.1). 3. The percentage of each metabolite to the total converted metabolites were not statistically significant between diseased periodontal tissue and pulp tissue. But the percentage of $LTB_4$ in pulp tissue was higher than that in diseased periodontal tissue(P<0.05). 4. The relative amounts of the total metabolites formed in lipoxygenase pathway to those formed in cyclo - oxygenase pathway were 6 fold in diseased periodontal tissue and 12 fold in pulp tissue. But there was no statistical significance between diseased periodontal tissue and pulp tissue(P>0.05).

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Carica papaya leaf water extract promotes innate immune response via MAPK signaling pathways

  • Hyun, Su Bin;Ko, Min Nyeong;Hyun, Chang-Gu
    • Journal of Applied Biological Chemistry
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    • v.64 no.3
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    • pp.277-284
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    • 2021
  • The emergence and rapid spread of the potentially fatal coronavirus disease 2019, caused due to infection by severe acute respiratory syndrome coronavirus-2, has led to worldwide interest in developing functional bioactive ingredients that act as immunomodulatory agents. In this study, we aimed to characterize Carica papaya extract and explore its potential as an immunomodulator by performing in vitro cell screening. Papaya leaf water extract (PLW) was found to significantly increase the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) by upregulating inducible nitric oxide synthase and cyclo-oxygenase-2 activity, respectively. Additionally, PLW increased the production of tumor necrosis factor-α and interleukin 1β in RAW 264.7 cells. Furthermore, PLW activated the expression of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase. These results indicate that PLW increased the production of NO, PGE2, and pro-inflammatory cytokines by activating the JNK and ERK pathways in macrophages, thus demonstrating immunomodulatory properties. Finally, high-performance liquid chromatography fingerprint analysis indicated the presence of rutin, narirutin, and ρ-coumaric acid in PLW (6.30, 119.76, and 47.25 ppm, respectively). Treating cells with these compounds at non-toxic concentrations had no effect on NO production. Taken together, these results suggest that PLW may have potential as an immunity-enhancing supplement.

Anti-inflammatory Activity of Peel Extracts in Color-fleshed Potatoes (컬러감자외피 추출물의 항염활성)

  • Nam, Jung-Hwan;Jeong, Jin-Cheol;Kwon, Oh-Keun;Hong, Su-Young;Kim, Su-Jeong;Soh, Hwang-Bae;Lee, Jong-Nam;Lee, Kyung-Tea;Park, Hee-Jhun
    • Korean Journal of Plant Resources
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    • v.26 no.5
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    • pp.533-538
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    • 2013
  • Potatoes were first introduced outside the Andes region four centuries ago, and have become an integral part of much of the world's food. Potatoes were first introduced into Europe in the 16th century and Korea in the early 19th century. In the nutritional aspects, potatoes contain abundant vitamins and minerals, as well as an assortment of phytochemicals such as carotenoids and natural phenols. Chlorogenic acid constitutes up to 90% of potato natural phenols. Due to the high content of potato functional compounds, it has known that potatoes are effective in the prevention of various human diseases. Recently, color-fleshed potatoes 'Hongyoung' and 'Jayoung' were developed by RDA, and it has reported that they have high content of anthocyanin. Additionally they show higher radical scavenging activity compared to white or yellow fleshed potatoes. So it will be expected that the consumption of color-fleshed potatoes grandually increase by pre-peeled potatoes and color potato chips. This study was conducted to enhance the peel of color-fleshed potatoes utilization and to determine the biological activity of peel of color-fleshed potatoes extract. The anti-inflammatory effects on ethanol extract and its solvent fraction were also evaluated. The anti-inflammatory activities of $CHCl_3$ fraction was evaluated for inhibitory activities against lipopolysacchride(LPS) induced nitric oxide(NO) and prostaglandin $E_2(PGE_2)$ production as well as inducible nitric oxide synthase(iNOS) and cyclo oxygenase-2(COX-2) protein expressions in RAW264.7 cell lines. The fraction inhibitory activity for both tests with $IC_{50}$ values showed in the ranges of $25{\sim}50{\mu}g/ml$. This result revealed that $CHCl_3$ fraction of Jayoung's peel is expected to be good candidate for development into source of anti-inflammatory agent.

Notochordal Cells Influence Gene Expression of Inflammatory Mediators of Annulus Fibrosus Cells in Proinflammatory Cytokines Stimulation

  • Moon, Hong-Joo;Joe, Hoon;Kwon, Taek-Hyun;Choi, Hye-Kyoung;Park, Youn-Kwan;Kim, Joo-Han
    • Journal of Korean Neurosurgical Society
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    • v.48 no.1
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    • pp.1-7
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    • 2010
  • Objective : Notochordal cells in the intervertebral disc interact with nucleus pulposus (NP) cells and support the maintenance of disc homeostasis by regulation of matrix production. However, the influence of notochordal cells has not been evaluated in the annulus fibrosus (AF), which is the primary pain generator in the disc. We hypothesized that the notochordal cell has the capacity to modulate inflammatory mediators secreted by AF cells secondary to stimulation. Methods : Notochordal and AF cells were isolated from adult New Zealand white rabbits. AF pellets were cultured with notochordal cell clusters or in notochordal cell-conditioned media (NCCM) for 24 or 48 hours with proinflammatory cytokines at varying concentrations. Gene expression in AF pellets were assayed for nitric oxide synthase (iNOS), cyclo-oxygenase (COX)-2, and interleukin (IL)-6 by real time reverse transcriptase polymerase chain reaction (RT-PCR). Results : AF pellet in NCCM significantly decreased the iNOS and COX-2 messenger ribonucleic acid (mRNA) levels compared to AF pellets alone and AF pellets with notochordal cells (p < 0.05). AF pellet resulted in dose-dependent iNOS and COX-2 expression in response to IL-$1{\beta}$, stimulation, demonstrating that 1 ng/ml for 24 hours yielded a maximal response. AF pellet in NCCM significantly decreased the expression of iNOS and COX-2 in response to 1ng/ml IL-$1{\beta}$, stimulation at 24 hours (p < 0.05). There was no difference in IL-6 expression compared to AF pellets alone or AF pellets with notochordal cell clusters. Conclusion : We conclude that soluble factors from notochordal cells mitigate the gene expression of inflammatory mediators in stimulated AF, as expected after annular injury, suggesting that notochordal cells could serve as a novel therapeutic approach in symptomatic disc development.

A STUDY ON ARACHIDONIC ACID METABOLISM OF CHRONIC PERIAPICAL LESIONS (만성 치근단주위 병소조직의 Arachidonic acid 대사에 관한 연구)

  • Park, Keum-Soon;Son, Ho-Hyun
    • Restorative Dentistry and Endodontics
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    • v.17 no.1
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    • pp.83-94
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    • 1992
  • This study was executed to measure the biosynthesis of arachidonic acid metabolic products in chronic periapical lesions, to compare the products among periapical granuloma, periapical cyst and chronic periapical abscess, and to understand the pathogensis of chronic periapical lesions. Tissues from 33 chronic periapical lesions of human teeth were enucleated during endodontic surgery. large part of each tissue was contained in liquid nitrogen immediately and the other was examined histologically. In histologically diagnosed 8 cases of periapical granuloma, 9 cases of periapical cyst and 8 cases of chronic periapical abscess. the tissues were homogenatecl and incubated with $_{14}C$-arachidonic acid. Lipid solvent extracts were separated by thin layer chromatography to be analyzed by autoradiography and TLC analyzer. 1. $TXB_2$, 6-keto-$PGF_1{\alpha}$ and $PGE_2$, $LTB_4$, HETEs, and unidentified product which are metabolic products of arachidonic acid were measured in the tissues of chronic peripaical lesions. 2. In all of periapical granuloma, cyst and abscess, the conversion rate of HETEs among all products was the highest(P<0.05), and the percentage of HETEs in total converted products was also the highest(P<0.05). 3. The concentration of each arachidonic acid product was higher in chronic periapical absecss than in periapical granuloma and cyst(P<0.05). The concentration of $TXB_2$ and HETEs in periapical cyst were hight than in periapical granuloma. 4. The relative amounts of total products from lipoxygenase pathway to those from cyclo-oxygenase pathway were about 7 fold in chronic periapical lesions. There was no difference among periapical granuloma, cyst and abscess(P<0.05). The total amount of products from each pathway were higher in chronic periapical abscess than in periapical cyst and granuloma.

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Anti-inflammatory Effect of Oxya chinensis sinuosa Ethanol Extract in LPS-induced RAW 264.7 Cells (LPS로 유도된 RAW 264.7세포에 대한 벼메뚜기(Oxya chinensis sinuosa) 에탄올 추출물의 항염증 효과)

  • Yoon, Young-Il;Chung, Mi Yeon;Hwang, Jae-Sam;Goo, Tae-Won;Ahn, Mi-Young;Lee, Young-Bo;Han, Myung-Sea;Yun, Eun-Young
    • Journal of Life Science
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    • v.24 no.4
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    • pp.370-376
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    • 2014
  • Although the grasshopper Oxya chinensis sinuosa has long been used as food in Korea, there is little data on its functional effects. In this study, we investigated the anti-inflammatory effect of O. c. sinuosa ethanol extract (OCE) in RAW 264.7 mouse macrophage cells treated with lipopolysaccharide (LPS) for induction of inflammation. First, we determined that there is no cytotoxicity at $2,000{\mu}g/ml$ or less of OCE in RAW 264.7 cells. To evaluate the anti-inflammatory effects of OCE, we investigated expression levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, and pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) in LPS-induced RAW 264.7 cells. In addition, we examined whether OCE could inhibit translocation of NF-${\kappa}B$ p65 into the nucleus in LPS induced RAW 264.7 cells. As a result, we found that the mRNA and protein levels of TNF-${\alpha}$ and IL-6 decreased in LPS-induced RAW 264.7 cells after treatment with OCE in a dose-dependent manner. In addition, we confirmed a $2,000{\mu}g/ml$ concentration of OCE inhibited translocation of NF-${\kappa}B$ p65 by immunnostaining and Western blot analysis, and a decrease in the protein expression levels of iNOS and COX-2. Accordingly, we suppose that OCE has an anti-inflammatory effect through down-regulation of TNF-${\alpha}$, IL-6, iNOS, and COX-2 related to ${\kappa}B$ p65 inflammatory signaling pathways.

All about pain pharmacology: what pain physicians should know

  • Kim, Kyung-Hoon;Seo, Hyo-Jung;Abdi, Salahadin;Huh, Billy
    • The Korean Journal of Pain
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    • v.33 no.2
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    • pp.108-120
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    • 2020
  • From the perspective of the definition of pain, pain can be divided into emotional and sensory components, which originate from potential and actual tissue damage, respectively. The pharmacologic treatment of the emotional pain component includes antianxiety drugs, antidepressants, and antipsychotics. The anti-anxiety drugs have anti-anxious, sedative, and somnolent effects. The antipsychotics are effective in patients with positive symptoms of psychosis. On the other hand, the sensory pain component can be divided into nociceptive and neuropathic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually applied for somatic and visceral nociceptive pain, respectively; anticonvulsants and antidepressants are administered for the treatment of neuropathic pain with positive and negative symptoms, respectively. The NSAIDs, which inhibit the cyclo-oxygenase pathway, exhibit anti-inflammatory, antipyretic, and analgesic effects; however, they have a therapeutic ceiling. The adverse reactions (ADRs) of the NSAIDs include gastrointestinal problems, generalized edema, and increased bleeding tendency. The opioids, which bind to the opioid receptors, present an analgesic effect only, without anti-inflammatory, antipyretic, or ceiling effects. The ADRs of the opioids start from itching and nausea/vomiting to cardiovascular and respiratory depression, as well as constipation. The anticonvulsants include carbamazepine, related to sodium channel blockade, and gabapentin and pregabalin, related to calcium blockade. The antidepressants show their analgesic actions mainly through inhibiting the reuptake of serotonin or norepinephrine. Most drugs, except NSAIDs, need an updose titration period. The principle of polypharmacy for analgesia in case of mixed components of pain is increasing therapeutic effects while reducing ADRs, based on the origin of the pain.

Effect of Suppressing the Activation of Macrophage Migration Inhibitory Factor by $Sambucus$ $williamsii$ $H_{ANCE}$ Extract & Pharmacopuncture Solution on Type II Collagen-induced Arthritis (접골목(接骨木)추출물 및 약침액에 의한 MIF 활성 조절능이 생쥐의 제2형 Collagen 유발 관절염에 미치는 영향)

  • Lee, Dong-Gun;Kim, Eun-Jung;Lee, Eun-Sol;Wang, Kai-Hsia;Cho, Hyun-Seok;Lee, Seung-Deok;Kim, Kap-Sung;Kim, Kyung-Ho
    • Journal of Acupuncture Research
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    • v.29 no.1
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    • pp.103-113
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    • 2012
  • Objectives : The purpose of this study is to evaluate effect of suppressing the expression of cyclo-oxygenase-type-2 (COX-2) as a consequence of inhibition macrophage migration inhibitory factor (MIF) activation by $Sambucus$ $williamsii$ $Hance$ (SWH) pharmacopunctureon rheumatoid arthritis (RA). Methods : In vitro test, synoviocytes extracted from type II collagen-induced arthritis (CIA) mouse's knee joint were cultivated After that, each well of synoviocytes was mixed with the extract of SWH at the dosage of $0.4mg/m{\ell}$, $0.6mg/m{\ell}$, $0.8mg/m{\ell}$, and $1.0mg/m{\ell}$ respectively, and cultivated for 24 hours after the addition. Reverse transcriptase - polymerase chain reaction (RT-PCR) is used to investigate the expression of MIF, Tumor necrosis factor (TNF)-${\alpha}$, COX-2 mRNA. $In$ $vivo$ test, thirty DBA female mice were used, and each ten mice were allocated into three group; normal group, CIA-elicitated group, and group treated with SWH pharmacopuncture on it's the point of $ST_{35}$ after CIA elicitation. It is investigated that change of mice foot thickness, histologic change of sliced synovial joint of mouse, and extent change of MIF, TNF-${\alpha}$, COX-2 in synovial membrane. Results : $In$ $vitro$ test, the expressions of cytokine(MIF, TNF-${\alpha}$, COX-2) mRNAs related to RA were dose-dependent decreased. In the SWH pharmacopuncture group, foot thickness and histologic change of sliced synovial joint were decreased comparing with CIA-elicitated group's change. In the SWH pharmacopuncture group, the suppression of MIF, TNF-${\alpha}$, COX-2 in synovial membrane was clearly shown comparing with CIA-elicitated group's change. Conclusions : It might be suggested that SWH pharmacopuncture mitigate tissue damage originated from rheumatoid arthritis by suppressing the expression of COX-2 as a consequence of inhibition MIF activation.

Suppression Effects of Sopunghwalhyeol-tang(Shufenghuoxie-tang) on the Monosodium Iodoacetate-induced Osteoarthritis in Rats (소풍활혈탕(疎風活血湯)이 Monosodium Iodoacetate로 유발한 흰쥐의 골관절염 억제에 미치는 영향)

  • Kim, Dae-Hyoung;Jeong, Su-Hyeon;Seo, Il-Bok;Kim, Soon-Joong
    • Journal of Korean Medicine Rehabilitation
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    • v.21 no.1
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    • pp.57-77
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    • 2011
  • Objectives : This study was to investigate the suppression effects of Sopunghwalhyeol-tang(Shufenghuoxie-tang) on the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Arthritis was induced by injection of monosodium iodoacetate(0.5 mg) into the both knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of Sopunghwalhyeol-tang(Shufenghuoxie-tang) by oraly for same duration. Normal group(n=8) was injected with normal saline and was taken distilled water for 20 days. Macroscopic examination and histopathological study on articular cartilage of knee joint were operated at 20 days after injection. Proteoglycan(PG) content of articular cartilages of knee joint was represented by safranine O staining, was measured at 20 days after injection. Tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$, in synovial fluid were measured with enzyme-linked immuno sorbent assay(ELISA) kit at 20 days after injection. Immunohistochemical staining of cyclo-oxygenase-2(COX-2), inducible nitric oxide synthase(iNOS) in knee joints were observed at 20 days after injection. Results : 1. Lymphocytes in peripheral blood the treated group was significantly decreased compared with the control group. 2. PG content in articular cartilage of the treated group was significantly increased compared with the control group. 3. Histopathologically, osteoarthritic scores of the treated group was significantly decreased compared with the control group. 4. $TNF-{\alpha}$ content in synovial fluid of the treated group was significantly decreased compared with the control group. 5. COX-2 revelation index in chondrocytes and synovial membrane of the treated group was significantly decreased compared with the control group. 6. Matrix metalloproteinase-3(MMP-3) revelation index in chondrocytes and synovial membrane of the treated group was significantly decreased compared with the control group. Conclusions : On the basis of these results, we concluded that Sopunghwalhyeol-tang(Shufenghuoxie-tang) has inhibiting effects on the $TNF-{\alpha}$, COX-2 and MMP-3 secretion of chondrocytes and synovial membrane in Monosodium Iodoacetate-induced osteoarthritis model of rats.