• The Korean Journal of Pain
• /
• v.35 no.3
• /
• pp.261-270
• /
• 2022

Background: The rostral ventromedial medulla (RVM) is a critical region for the management of nociception. The RVM is also involved in learning and memory processes due to its relationship with the hippocampus. The purpose of the present study was to investigate the molecular mechanisms behind orexin-A signaling in the RVM and hippocampus's effects on capsaicin-induced pulpal nociception and cognitive impairments in rats. Methods: Capsaicin (100 g) was applied intradentally to male Wistar rats to induce inflammatory pulpal nociception. Orexin-A and an orexin-1 receptor antagonist (SB-334867) were then microinjected into the RVM. Immunoblotting and immunofluorescence staining were used to check the levels of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) in the RVM and hippocampus. Results: Interdental capsaicin treatment resulted in nociceptive responses as well as a reduction in spatial learning and memory. Additionally, it resulted in decreased BDNF and increased COX-2 expression levels. Orexin-A administration (50 pmol/1 µL/rat) could reverse such molecular changes. SB-334867 microinjection (80 nM/1 µL/rat) suppressed orexin's effects. Conclusions: Orexin-A signaling in the RVM and hippocampus modulates capsaicin-induced pulpal nociception in male rats by increasing BDNF expression and decreasing COX-2 expression.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.248.3-249
• /
• 2003

A series of tetrahydroaminoacridine and their analogues were synthesized. Tetrahydroaminoacridine(tacrine) is an anticholinesterase agent used in the treatment of Alzheimer's disease. Introduction of piperidine group at the para position enhanced anti-inflamatory activity for Alzheimer's disease. We investigated their ability to inhibit cyclooxygenase-1 and 2 isoforms. (omitted)

• Biomolecules & Therapeutics
• /
• v.14 no.1
• /
• pp.11-18
• /
• 2006

Certain flavonoids possess anti-inflammatory activity. Besides their antioxidative property, the cellular action mechanisms of flavonoids include an inhibition of arachidonate metabolizing enzymes such as cyclooxygenases and lipoxygenases, and a down-regulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-$\alpha$. In this review, the recent findings of anti-inflammatory flavonoid research since 2004 were summarized. And the cellular mechanisms on signal transduction pathways were also discussed.

• Radiation Oncology Journal
• /
• v.21 no.3
• /
• pp.216-221
• /
• 2003

Purpose: To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over- and under-expressing COX-2. Materials and Methods: A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and $10\%$ fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment with radiation and/or celecoxib. Results: Celecoxib enhanced the radiation sensitivity of the A549 cells in the medium containing the $10\%$ FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with $30\muM\;and\;50\muM$ celecoxib. This enhanced radiosensitivity disappeared in the medium containing the $1\%$ FBS. Celecoxib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Conclwsion: Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent.

• BMB Reports
• /
• v.42 no.9
• /
• pp.552-560
• /
• 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 Korean Medicine Rehabilitation
• /
• v.18 no.1
• /
• pp.65-74
• /
• 2008

Objectives : This experimental study was designed to investigate the effects of Lumbricus extract (LE) on the changes in regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, and further to determine the mechanism of action of LE. Methods : The changes of rCBF were observed by Laser-Doppler flowmetry (LDF) and the changes of MABP were recorded by a data acquisition system assembled with MacLab and Macintosh. Results : LE significantly increased rCBF in a high dosage(10.0 mg/kg, i.p), but MABP was somewhat increased as compared with baseline. This result suggests that LE significantly increased rCBF by dilating pial arterial diameter. Increase of LE-induced rCBF was significantly inhibited by pretreatment with indomethacin (1 mg/kg, i.p), an inhibitor of cyclooxygenase, but was not significantly inhibited by pretreatment with methylene blue ($10{\mu}g/kg$, i.p), an inhibitor of guanylate cyclase. Conclusions : LE increased rCBF by dilating pial arterial diameter, and the action of this response was mediated by cyclooxygenase.

• The Korean Journal of Physiology and Pharmacology
• /
• v.5 no.3
• /
• pp.253-258
• /
• 2001

The present study was aimed to examine whether the expression of renin is associated with that of cyclooxygenase-2 (COX-2) in the kidney. Male Sprague-Dawley rats were made two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertensive, to stimulate or to inhibit the endogenous renin-angiotensin system, respectively. The expression of renin and COX-2 mRNA was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. 2K1C hypertensive rats showed an increased expression of renin as well as of COX-2 in the clipped kidney. The expression of renin was decreased in parallel with that of COX-2 in the contralateral non-clipped kidney. Removal of the renal arterial clip reversed the expression of both genes, along with the blood pressure, to the control level. On the other hand, DOCA-salt hypertension was associated with parallel decreases of renin and COX-2 expression. These results indicate that renin and COX-2 genes are coordinately expressed in the kidney.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.6
• /
• pp.1340-1347
• /
• 2024

Ehretia asperula is a medicinal plant of the Ehretiaceae family used to treat inflammatory disorders, but the underlying mechanisms are not fully elucidated. The anti-inflammatory potential was determined based on enzyme cyclooxygenase-2 (COX-2) inhibition, which showed that the 95% ethanol extract (95ECH) was most effective with a half-maximal inhibitory concentration (IC₅₀) value of 34.09 ㎍/mL. The effects of 95ECH on phagocytosis, NO production, gene, and protein expression of the cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) and inducible nitric oxide synthase/ nitric oxide (iNOS/NO) pathways in lipopolysaccharide (LPS)-induced RAW264.7 cells were examined using the neutral red uptake and Griess assays, reverse-transcriptase polymerase chain reactions (RT-PCR), and enzyme-linked immunosorbent assays (ELISA). The results showed that 95ECH suppressed phagocytosis and the NO production in activated macrophage cells (p < 0.01). Conversely, 95ECH regulated the expression levels of mRNAs for cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) as well as the corresponding proteins. In addition, PGE2 production was inhibited in a dose-dependent manner by 95ECH, and the expression of iNOS and COX-2 mRNAs was decreased in activated macrophage cells, as expected. Therefore, 95ECH from E. asperula leaves contains potentially valuable compounds for use in inflammation management.

• Korean Journal of Food Science and Technology
• /
• v.43 no.1
• /
• pp.110-113
• /
• 2011

Egg allergies are the most prevalent food hypersensitivity in children. The major egg allergens are proteins, such as ovalbumin (OVA) and ovomucoid (OVM), which are mainly contained in egg whites. OVA is the major protein in egg white, comprising 54% of the total protein content. OVA has been widely used in experimental inhalant and dietary allergy animal models, but its mechanism has not been clearly identified. In this study, we showed that OVA induced nuclear factor-${\kappa}B$ activation. OVA also induced the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These data suggest new approaches for developing efficient anti-allergic strategies.

• Journal of Applied Biological Chemistry
• /
• v.64 no.4
• /
• pp.375-382
• /
• 2021

Biorenovation is a microbial enzyme-based structural modification of component compounds in natural products and synthetic compounds including plant extracts with the potential benefits of improved biological activities compared with its reaction substrates. In this study, we investigated the anti-inflammatory activity of Distylium racemosum leaf extract and D. racemosum leaf biorenovation extract (DLB). As a result, DLB inhibited nitric oxide, prostaglandin E2, and inflammatory cytokines including tumor necrosis factor-α, interleukin-6, interleukin-1β at non-toxic concentrations. In addition, DLB significantly inhibited inducible nitric oxide synthase and cyclooxygenase-2 on LPS-treated RAW 264.7 macrophages. Based on these results, we suggest that the DLB could be used as a potent anti-inflammatory agents. It also suggests that the application of biological evolution has potential usefulness to increase the practical value of natural products.