• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.83-91
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• 1999

Angiotensin II (ANG II) has a biphasic effect on $Na^+$ transport in proximal tubule: low doses of ANG II increase the $Na^+$ transport, whereas high doses of ANG II inhibit it. However, the mechanisms of high dose ANG II-induced inhibition on $Na^+$ uptake are poorly understood. Thus the aim of the present study was to investigate signal transduction pathways involved in the ANG II-induced inhibition of $Na^+$ uptake in the primary cultured rabbit renal proximal tubule cells (PTCs) in hormonally defined serum-free medium. ANG II $(10^{-9}\;M)-induced$ inhibition of $Na^+$ uptake was blocked by losartan $(10^{-8}\;M,\;AT_1\;antagonist),$ but not by PD123319 $(10^{-8}\;M,\;AT_2\;antagonist)$ (P<0.05). ANG II-induced inhibition of $Na^+$ uptake was also completely abolished by neomycin $(10^{-4}\;M,$ PLC inhibitor), W-7 $(10^{-4}\;M,$ calmodulin antagonist), and $AACOCF_3\;(10^{-6}\;M,\;PLA_2\;inhibitor)$ (P<0.05). ANG II significantly increased $[^3H]arachidonic$ acid (AA) release compared to control. The ANG II-induced $[^3H]AA$ release was blocked by losartan, $AACOCF_3,$ neomycin, and W-7, but not by PD123319. ANG II-induced $[^3H]AA$ release in the presence of extracellular $Ca^{2+}$ was greater than in $Ca^{2+}-free$ medium, and it was partially blocked by TMB-8 $(10^{-4}\;M,$ intracelluar $Ca^{2+}$ mobilization blocker). However, in the absence of extracellular $Ca^{2+},$ it was completely blocked by TMB-8. In addition, econazole $(10^{-6}\;M,$ cytochrome P-450 monooxygenase inhibitor) and indomethacin $(10^{-6}\;M,$ cyclooxygenase inhibitor) blocked ANG II-induced inhibition of $Na^+$ uptake, but NGDA $(10^{-6}\;M,$ lipoxygenase inhibitor) did not affect it. In conclusion, $PLA_2-mediated$ AA release is involved in ANG II-induced inhibition of $Na^+$ uptake and is modulated by $[Ca^{2+}]_i$ in the PTCs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.740-746
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• 2004

In order to identify the anti-inflammatory and analgesic properties of natural herbal extracts, widely used in the Korean traditional medicine, an in vitro screening system was designed using pGL3, a luciferase reporter vector, and the tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-II as target genes. The promoter regions of each gene was generated by PCR using the human chromosome as template DNA, and inserted into pGL3 vector with Kpnl and Hindlll. The final construct was transfected into human myleomonocytic leukemia cells (U937) that could be differentiated and activated by phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). Using this system, we tested the anti-inflammatory and analgesic effects of several herbal extracts being regarded to have the medicinal effects of diminishing the body heat and complementing Qi. The well-known chemicals of PD98059 and berberine chloride were used as controls of the transcriptional inhibitors of TNF-α and COX-II, respectively. Among them, Salvia miltiorrhiza (Dan-Sam) was found to exhibit the significant medicinal properties of anti-inflammatory and analgesic effects.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.3
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• pp.241-262
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• 2009

Objectives This study is designed to investigate the effects of Jujadokseo-hwan on the brain ability and inducing oxidative stresses. Methods We measured the changes of regional cerebral blood flow and mean arterial blood pressure. Then we analyzed histological examination, immunohistochemistric response and anti-oxidant activity of Jujadokseo-hwan. Results 1. Treatment of Jujadokseo-hwan significantly increased regional cerebral blood flow but decreased mean arterial blood pressure. 2. Treatment of Jujadokseo-hwan-induced increase of regional cerebral blood flow was significantly inhibited by pretreatment with indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase. 3. In histological examination through TTC stain, group I was no change, but group II showed that discolored in the most cortical part. Group III showed that decreased discolor in the cortical part. 4. In immunohistochemistric response of BDNF, group II showed that lower response effect. Group III showed that increase response effect. 5. Treatment of Jujadokseo-hwan increased proliferation rates of Glial cell effectively 6. Treatment of Jujadokseo-hwan accelerated proliferation rates of C6 cells in vitro. In addition, protective effects on cell death induced by paraquat, rotenone and hydrogen peroxide. In addition, activity of SOD were increased by treatment with Jujadokseo-hwan. Conclusions In conclusion, Jujadokseo-hwan can improve of the brain ability, learning ability, memory ability and induce ischemic brain injuries.

• Journal of the Korean Chemical Society
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• v.62 no.5
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• pp.352-357
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• 2018

Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide) is a cyclooxygenase-2 inhibitor used in the treatment of arthritis, acute pain, and dysmenorrhoea. Celecoxib is a Biopharmaceutics Classification System (BCS) class II compound whose oral bioavailability is highly limited owing to its poor aqueous solubility. Several polymorphs of celecoxib have been identified as Form I, Form II, and Form III with melting points of about $162.8^{\circ}C$, $161.5^{\circ}C$, and $160.8^{\circ}C$, respectively. Form IV was generated from the precipitated suspension in the presence of HPMC (Hydroxypropyl methylcellulose) and Polysorbate 80. A rapid rate of dissolution is useful because the rate of dissolution of a drug typically increases its bioavailability. The aim of this study was to investigate the possibility of production of new crystal form of celecoxib that has higher solubility than Form III. New crystal form of celecoxib (Form A) has been isolated by recrystallization and characterized by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis and powder X-ray diffractometry (PXRD). Form A was dissolved faster than Form III. At 30 minutes, the dissolution of Form A was 97.3%, whereas the dissolution of Form III was 82.2% (p < 0.1). After storage of three months at $20^{\circ}C$, in 24% RH (Relative Humidity), the crystal form was not transformed.

• The Journal of Korean Physical Therapy
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• v.21 no.2
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• pp.117-124
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• 2009

Purpose: This study examined the effects of swimming exercise and Achyranthes Radix extracts on the inflammatory and behavioral responses in type II collagen-induced arthritic rats for 28 days. Methods: Sprague-Dawley rats were allocated randomly to one of the following four groups: only type II collageninduced (group Ⅰ), application of swimming exercise after type II collagen-induced (group II), application of Achyranthes Radix ointment after type II collagen-induced (group III), application of swimming exercise and Achyranthes Radix ointment after type II collagen-induced (group IV). Arthritis was established in SD rats by an intradermal injection of Chick type II collagen plus incomplete Freund's adjuvant at the base of the tail of the animals. The swimming exercise program consisted of a 25 min swimming session/day with a load corresponding to 5.5% of the weight bearing, three days/week for four weeks. The Achyranthes Radix ointment (0.1g) was applied twice a day for five days. The changes in behavior, H & E stain, and cyclooxygenase-2 (COX-2) level in the knee joint were assessed. Results: The gross and histological examination, after RA induction showed reddening, edema and erythema. The H & E stain revealed the destruction of articular cartilage, bony erosion and the infiltration of inflammatory cells after RA induction. The mechanical allodynia test results were significantly higher in group I than in groups II, III and IV (p<0.01). The immunohistochemistrical response of COX-2 in the knee joint showed that groups II, III, IV had a lower response effect than group I. Conclusion: Swimming exercise training and Achyranthes Radix ointment decreased the inflammatory responses and enhanced the behavioral responses in the arthritic rats.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.5
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• pp.395-402
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• 2020

This study has investigated the effect of a potent bioflavonoid, troxerutin, on diabetes-induced changes in pro-inflammatory mediators and expression of microRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissue of type-I diabetic rats. Male Wistar rats were randomly divided into four groups (n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10 weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment. Inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II (COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samples by enzyme-linked immunosorbent assay. Gene expressions for transcription factor NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associated factor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerase chain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1, TRAF-6, NF-κB, and protein levels of cytokines IL-1β, IL-6, TNF-α, adhesion molecules ICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a as compared with healthy rats (p < 0.05 to p < 0.01). However, one month treatment of diabetic rats with troxerutin restored glucose and insulin levels, significantly decreased expression of inflammatory genes and pro-inflammatory mediators and increased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). In healthy rats, troxerutin had significant reducing effect only on NF-κB, TNF-α and COX-II levels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin prevented the activation of NF-κB-dependent inflammatory signaling in the aorta of diabetic rats, and this response may be regulated by microRNA-146a.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.122-126
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• 1996

In vitro inhibitory effect of aspalatone ((3-(2-methyl-4-pyronyl)]-2-acetyloxybenzoate) on collagen-, ADP-, and epinephrine-induced platelet aggregation in human platelet rich plasma (PRP) was compared with the effects of reference drugs (acetylsalicylic acid, cilostazol and ticlopidine). Aspalatone inhibited time and dose dependently human platelet aggregation induced by collagen; relative potency was in the order of cilostazol>acetylsalicylic acid>aspalatone>ticlopidine. Aspalatone, like acetylsalicylic acid, potently inhibited only the secondary phase of ADP-and epinephrine-induced aggregation. Thromboxane $B^2$ production evoked by collagen in human PRP was inhibited significantly and concentration-dependently by aspalatone and acetylsalicylic acid. These results were in agreement with the earlier studies in which the antiplatelet action of aspalatone was indicated to be due to the inhibition of platelet cyclooxygenase activity (Han et al., Arzneim. Forsch./Drug Res. 44(II), 1122, 1994; Suh and Han, Yakhak Hoeji 39, 565, 1995). In addition, the inhibitory activity of aspalatone on the platelet aggregation appears to be inversely related to the rate of nonspecific deacetylation of the drug in plasma.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.381-385
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• 2019

We attempted to examine anti-inflammatory and anti-oxidant effects of 4'-O-${\beta}$-D-glucosyl-5-O-methylvisamminol (GOMV), the first epigenetic inhibitor of histone phosphorylation at Ser10. While GOMV did not affect the viability of murine macrophage RAW 264.7 cells, it significantly suppressed lipopolysaccharide (LPS)-induced generation of prostaglandin $E_2$ ($PGE_2$) and nitric oxide (NO) through transcriptional inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). GOMV also scavenged free radicals in vitro, increased NF-E2-related factor 2 (NRF2), and activated antioxidant response element (ARE), thereby resulting in the induction of phase II cytoprotective enzymes in human keratinocyte HaCaT cells. Finally, GOMV significantly protected HaCaT cells against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative intracellular damages. Together, our results illustrate that GOMV possesses anti-inflammatory and anti-oxidant activity.

• IMMUNE NETWORK
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• v.10 no.3
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• pp.92-98
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• 2010

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs). Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells. Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs. Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.