• Toxicological Research
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• v.19 no.1
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• pp.33-37
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• 2003

Asiaticoside has been tested for the ability as an anti-inflammatory drug using lipopolysaccharide (LPS)-stimulated macrophage cell line (RAW 264.7 cell). LPS treatment induced dramatically inducible nitric oxide synthase (iNOS) in RAW cells. However, asiaticoside inhibited LPS-stimulated iNOS induction in a concentration-dependent manner. Especially, higher concentrations (＞50 $\mu\textrm{M}$) of asiaticoside completely blocked iNOS induction. In addition, LPS-stimulated expression of inducible cyclooxygenase (COX-2) and interleukin-1 $\alpha$ (IL-1 $\alpha$) was inhibited by asiaticoside treatment. Asiaticoside up to 50 $\mu\textrm{M}$ still required to inhibit COX-2 and IL-1 $\alpha$ induced by LPS. Consistent with these findings, treatment with asiaticoside suppressed do novo synthesis and cellular accumulation of prostaglandin $E_2$ to a lesser extent, suggesting that asiaticoside blocked the induction as well as the activity of COX-2 These results suggest the possibility that asiaticoside may be effective therapeutic agents for septic shock and other inflammatory diseases.

• 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.

• Journal of Korean Physical Therapy Science
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• v.9 no.1
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• pp.89-94
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• 2002

Prostaglandins are generated through two isoforms of the enzyme cyclooxygenase, constitutively expressed cyclooxygenase(COX)-1 and COX-2, which is induced at sites of inflammation. Inhibition of COX-2 is desirable as this may avoid side effects seen with NSAIDs. We examined the effects of transcutaneous electrical nerve stimulation and cold therapy on the levels of muscle cycloooxygenase-2 mRNA in rats of carrageenan-induced inflammatory. The method of behavioral assessment were paw withdrawal latency(PWL) and tail flick test(TFT). The COX-2 mRNA levels were quantified by reverse transcription-polymerase chain reaction (RT-PCR). Following the transcutaneous electrical nerve stimulation and cold therapy, PWL and TFT were increased and COX-2 mRNA expression in gastrocnemius muscles were decreased. These results suggest that a transcutaneous electrical nerve stimulation and cold therapy were good therapy for a muscle pain.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.139-140
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• 2003

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.80-80
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• 2002

• Biomedical Science Letters
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• v.9 no.3
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• pp.123-131
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• 2003

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study hypothesized that a vascular infection with cytomegalovirus (CMV) may induce a chronic inflammatory reaction and activated inflammatory cells may express inflammatory mediators such as cyclooxygenase-2 (COX-2) and matrix metalloproteinases-9 (MMP-9). To confirm the hypothesis, the immunohistochemical stains for CMV late antigen, COX-2, MMP-9, macrophage, and T-lymphocyte were performed on CMV-infected atherosclerotic lesions. The immunoreactivity for COX-2 and MMP-9 was evident in all cases of atherosclerosis along with plaques, mainly in macrophages/foamy cells, intimal and medial smooth muscle cells, and endothelial cells of the intima. Within the intima, the increased immunoreactivity for COX-2 and MMP-9 was colocalized to the area stained with CMV late antigen. Sections from control specimens showed no immunoreactivity for CMV late antigen, COX-2 and MMP-9. These data seem to support the hypothesis that CMV may participate in a pathogenetic mechanism for atherogenesis or progression of atherosclerosis.

• Natural Product Sciences
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• v.2 no.1
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• pp.56-74
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• 1996

Prostaglandin $H_2$ synthase is the pharmacological target site of nonsteroidal antiinflammatory drugs. Inhibitory effects on cyclooxygenase activity of the synthase by extracts prepared from herbal medicines and wild plants in Korea have been estimated. Sixteen species out of 612 species exhibited more than 50% of inhibition on the enzyme activity. The active extracts prepared from Carex humilis, Celastrus orbiculatus, Eugenia caryophyllata, Gleditsia japonica var. koraiensis, Glycyrrhiza grabra, Glycyrrhiza uralensis, Gyrophora exculenta, Lespedeza maximowiczii, Morus alba, Persicaria conspicua, Prunus salicina, pterocarya stenoptera, Rheum undulatum, Vitis amurensis, and Vitis coignetiae have been sequentially washed with methylene chloride, ethyl acetate, n-butanol. Among the solvent fractions of the active herbal extracts, ethyl acetate fraction of Carex humilis exhibited the highest inhibitory effect on the cyclooxygenase activity of prostaglandin $H_2$ synthase.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.241-249
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• 1998

Platelet-activating factor(PAF) enhanced interleukin-1(IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide(LPS). After 24h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with $IC_{50}\;of\;2\;{\mu}M\;and\;5\;{\mu}M$, respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at $1\;{\mu}M\;and\;5\;{\mu}M$, respectively. In addition, leukotriene $B_4$ and prostaglandin $E_2$ production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAF- stimulated leukotriene $B_4$ and prostaglandin $E_2$ production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium-sensitive dye fura-2 at the single cell level. PAF at any dose between $10^{-16}\;and\;10^{-8}$ M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium level when PAF was added to alveolar macrophages in the presence of LPS or LPS+LTB4, and 4, 24 and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lipoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.

• Natural Product Sciences
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• v.3 no.1
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• pp.19-28
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• 1997

Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible cyclooxygenase (COX-II) is induced by some cytokines, mitogens, and endotoxin presumably in pathological conditions such as inflammation. We have evaluated the inhibitory effects of solvent fractionated extracts of natural products on the activities of COX-I and COX-II. Oxygen uptake COX assay was performed, as a primary screening from the tissue extracts of bovine seminal vesicles (BSV), by monitoring the initial rate of oxygen uptake using an oxygen electrode. Additionally, we evaluated plant extracts for the inhibitory effects of COX-I (in HEL cells) and COX-II (in lipopolysaccharide activated J774A.1 macrophages) using thin layer chromatography of prostanoids produced from $^{14}C-labelled$ arachidonic acid (AA). The use of such models of COX-I and COX-II assay will lead to the identification of specific inhibitors of cyclooxygenases with presumably less side effects than present therapies. Inhibitory effects of 50 kinds of plant extracts on the COX-I and COX-II activities were determined and the active fractions were found in the ethyl acetate fractions of Dryopteris crassirhizoma (roots), Amomum cardamomum (roots), Triticum aestivum (seeds), Perilla sikokiana (leaves), Anemarrhena asphodeloides (roots). Especially, the ethyl acetate fraction of Dryopteris crassirhizoma (roots), which exhibited the strong inhibition against BSV COX $(IC_{50},\;65.4\;{\mu}g/ml)$, COX-I $(IC_{50},\;8.5\;{\mu}g/ml)$, and COX-II $(IC_{50},\;17.2\;{\mu}g/ml)$, is under investigation to isolate active principles using activity-guided fractionation method.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.749-752
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• 2005

We investigated the effects of electroacupuncture (EA) on the expression of cyclooxygenase in the spinal cord of acute inflammatory pain model. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw of Sprague-Dawley. Bilateral 2 Hz EA stimulation with 0.5 mA, 1 mA and 3 mA were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles in carrageenan-injected rats. Three hours after carrageenan injection, effects of EA on cyclooxygenase (COX) expression were observed in the dorsal horn of the spinal cord using immunohistochemical method. The immunoreaction of COX-1 tended to increase in the superficial laminae and the neck of the dorsal horn as compared with normal. The COX-2 immunoreaction in the carrageenan-injected rat was also significantly increased in the all regions of the dorsal horn as compared with normal one. However, COX-1 immunoreaction in carrageenan-injected rat were decreased in the superficial laminae and neck of the dorsal horn by low intensity of EA stimulation. Except high intensity of EA stimulation in the superficial laminae, COX-2 expression was attenuated in all regions of the dorsal horn by all types of EA treatment. It is concluded that EA treatment may attenuate inflammatory pain in carrageenan-injected rat through modulating expression of COX-2 in the dorsal horn of the spinal cord.