• Natural Product Sciences
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• v.2 no.1
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• pp.48-55
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• 1996

The CINC-1 is a member of rat interleukin-8 with chemotactic and activating properties to neutrophils. The CINC-1 induction in LPS-stimulated rat peritoneal macrophages was analyzed using a sensitive enzyme-linked immunosorbent assay. The peritoneal macrophages contained about 3 ng/ml as a basal level, and induced to maximal 18 ng/ml of CINC-1 by stimulation with 5 ${\mu}g/ml$ of LPS. Antiinflammatory steroids of dexamethasone and triamcinolon significantly suppressed the CINC-1 induction, where as aspirin and idomethacin did not show suppression. Inhibitory effects on the CINC-1 induction by natural triterpenoids having steroidal structures were analyzed. Among the 39 kinds of triterpenoids isolated from herbal medicines, acacigenin B and nigaichigoside F1 exhibited the highest suppression on the CINC-1 induction.

• Herbal Formula Science
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• v.12 no.1
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• pp.247-254
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• 2004

Objective: Effects of keumengja extracts on the blood picture in rat were determined. Results: Values of RBC, PCV and Hb showed a high in keumenja groups, however the values of PCV and Hb showed no significantly different in keumenja groups. Counts of WBC showed no significantly different in all treatment groups. In the composition of WBC neutrophils showed a tendance to decrease in keumengja groups, however these values showed no significantly different. Lymphocytes showed a high portion in keumengja groups and this portion showed a tendance to increase to increased concentration of keumengja. The portion of monocytes and basophils showed no significantly different in all treatment groups. Eosinophils showed a tendance to decrease in keumengja groups.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.383-388
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• 1998

The present study was aimed to investigate the preventive effects of rebamipide on the multiple organ dysfunction in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide; LPS) in comparison with that of methotrexate. Endotoxemia for 6 hours resulted in little change in the levels of hemoglobin and neutrophils. However, treatment with methotrexate decreased significantly the numbers of circulating neutrophils. Significant increases in serum alanine aminotransferase (ALT,958 $\pm$ 250 lU/L, p<0.001) and aspartate aminotransferase (AST, 1350 $\pm$ 295 lU/L, p<0.001) levels induced by endotoxemia were significantly decreased by rebamipide and methotrexate. The increased level of lactic acid dehydrogenase (LDH) by LPS (2850 $\pm$ 467 lU/L, p<0.05) was significantly inhibited by rebamipide, but not by methot.elate. The elevated serum creatinine (1.2$\pm$0.1, p.0.05) and urea levels (55.3$\pm$6.5 mg/dL, p.0.01) by LPS were also decreased by rebamipide, but not by methotrexate. In line with these results, the plasma concentration of tumor necrosis factor-$\alpha$ (TNF-7,167 $\pm$ 20 pg/mL) was significantly increased upon injection of endotoxin at 1 hour by 1570$\pm$100 pg/mL, and declined to 312$\pm$35 pg/mL at 6 hours. The TNF-$\alpha$ level at 6 hours was significantly decreased by rebamipide to 207$\pm$8 pg/mL (P<0.05). Taken together, it is summarized that rebamipide inhibits the development of multiple ogran dysfunction by inhibition of neutrophil activation in association with inhibition of TNF-$\alpha$ formation in a murine model of endotoxemia.

• Natural Product Sciences
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• v.3 no.1
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• pp.59-70
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• 1997

A rat chemokine, cytokine-induced neutrophil chemoattractant-1 (CINC-1) has chemotactic and activating properties to neutrophils. Rat kidney epithelioid NRK-52E cells contained 4 ng/ml of ClNC-1 as a basal level and their CINC-1 production was significantly increased by stimulation with lipopolysaccharide (LPS) of E. coli. Maximal induction of ClNC-1 was 58 ng/ml when 3 ${\mu}g/ml$ of LPS was treated to the NRK-52E cells. Inhibitory effects on CINC-1 induction in LPS-stimulated NRK-52E cells by extracts prepared from herbal medicines and wild plants in Korea were analyzed. At the final concentration of 100 ${\mu}g/ml$ , 9 species out of 304 species of herbal extracts exhibited more than 50% of inhibition on the CINC-1 induction. The active extracts prepared from Artemisia argyi, Lythrum salicaria, Machilus thunbergii, Magnolia sieboldii, Nelumbo nucifera, Prunus persica, Rubus coreanus, Sanguisorba officinalis, and Tripterygium regelii have been sequentially fractionated to obtain methylene chloride, ethyl acetate, butanol, and aqueous layers. Among solvent fractions of the active herbal extracts, methylene chloride fractions of Artemisia argyi and Magnolia sieboldii exhibited the highest inhibitory effects on CINC-1 induction in LPS-stimulated NRK-52E cells.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.233-239
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• 1998

Stimulated alveolar macrophages and neutrophils produce nitric oxide, a free radical by an inducible nitric oxide synthase(iNOS), which reacts with superoxide anion to form peroxynitrite, a more highly reactive toxic species. The objectives of the present study were to evaluate acute inflammatory lung injury and to determine iNOS mRNA induction and nitric oxide production by rat broncho-alveolar lavage cells following intratracheal treatment of silica. After 4 h exposure to silica, differential counts of broncho-alveolar lavage cells and lactate dehydrogenase(LDH) activity as well as total protein in the broncho-alveolar lavage fluid were determined. Broncho-alveolar lavage cells were also assayed for iNOS mRNA and the productions of nitrite and nitrate measured in the cells cultured. Differential analysis of broncho-alveolar lavage cells showed that the number of alveolar macrophages slightly decreased following silica treatment; however, red blood cells, lymphocytes, and neutrophils significantly were increased by 9-, 14-, and 119-fold following silica treatment, respectively, compared with the saline control. It was also found significant increases in the LDH activity and total protein in the lavage fluid obtained from silica-treated rats, indicating silica-induced acute lung injury. Northern blot analysis demonstrated that the steady state levels of iNOS mRNA in broncho-alveolar lavage cells were increased following silica treatment. The productions of nitrite and nitrate in the cultured cells were significantly increased by 2-fold following silica treatment, respectively, which were attenuated by the NOS inhibitor $N{\omega}-nitro-L-arginine-methyl$ ester(L-NAME) and partially reversed by L-arginine. These findings suggest that nitric oxide production in alveolar macrophages and recruited neutrophils is increased in response to silica. Nitric oxide may contribute in part to acute inflammatory lung injury.

• The Journal of Korean Medicine
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• v.16 no.1 s.29
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• pp.271-280
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• 1995

Effects of aqua-acupuncture with soshiho-tang at Kansu(BL_{18}$) and Tamsu(BL_{19}$) on the Glutamic Oxaloacetic Transaminase(GOT), Glutamic Pyruvic Transaminase(GPT), Lactic dehydrogenase(LDH) and blood pictures in rat with $CCI_4$ were determined. In the group with $CCI_4$ the activity of GOT, GPT and LDH showed a tendency to increase, however these values showed a tendency to decrease by the aqua-acupuncture with soshiho-tang throughout experimental days and these values were recovered to those of control group on the last experimental days. Counts of RBC and Hemoglobin showed a tendency to decrease in rat with $CCI_4$, however these decreased values were recovered by the aqua-acupuncture with soshiho-tang and on the last experimental days, these values were similar to those of control group. In the $CCI_4$ group, counts of WBC and the proportion of Lymphocytes showed a tendency to increase and the proportion of Neutrophils showed a tendency to decrease, however these values showed a rapid recovery by the aqua-acupuncture with soshiho-tang. In the meridian point of Kansu and Tamsu, the effects of aqua-acupuncture with soshiho-tang on recovery of liver function showed no difference. Results from this study indicate that the aqua-acupuncture with soshiho-tang can improve the liver function in rat with $CCI_4$.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.617-628
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• 1998

In order to understand the pathogenetic mechanism of adult respiratory distress syndrome (ARDS), the role of phospholipase A2 (PLA2) in association with oxidative stress was investigated in rats. $Interleukin-1{\alpha}\;(IL-1,\;50\;{\mu}g/rat)$ was used to induce acute lung injury by neutrophilic respiratory burst. Five hours after IL-1 insufflation into trachea, microvascular integrity was disrupted, and protein leakage into the alveolar lumen was followed. An infiltration of neutrophils was clearly observed after IL-1 treatment. It was the origin of the generation of oxygen radicals causing oxidative stress in the lung. IL-1 increased tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC) in the bronchoalveolar lavage fluid, but mepacrine, a PLA2 inhibitor, did not change the levels of these cytokines. Although IL-1 increased PLA2 activity time-dependently, mepacrine inhibited the activity almost completely. Activation of PLA2 elevated leukotriene C4 and B4 (LTC4 and LTB4), and 6-keto-prostaglandin $F2{\alpha}\;(6-keto-PGF2{\alpha})$ was consumed completely by respiratory burst induced by IL-1. Mepacrine did not alter these changes in the contents of lipid mediators. To estimate the functional changes of alveolar barrier during the oxidative stress, quantitative changes of pulmonary surfactant, activity of gamma glutamyltransferase (GGT), and ultrastructural changes were examined. IL-1 increased the level of phospholipid in the bronchoalveolar lavage (BAL) fluid, which seemed to be caused by abnormal, pathological release of lamellar bodies into the alveolar lumen. Mepacrine recovered the amount of surfactant up to control level. IL-1 decreased GGT activity, while mepacrine restored it. In ultrastructural study, when treated with IL-1, marked necroses of endothelial cells and type II pneumocytes were observed, while mepacrine inhibited these pathological changes. In histochemical electron microscopy, increased generation of oxidants was identified around neutrophils and in the cytoplasm of type II pneumocytes. Mepacrine reduced the generation of oxidants in the tissue produced by neutrophilic respiratory burst. In immunoelectron microscopic study, PLA2 was identified in the cytoplasm of the type II pneumocytes after IL-1 treatment, but mepacrine diminished PLA2 particles in the cytoplasm of the type II pneumocyte. Based on these experimental results, it is suggested that PLA2 plays a pivotal role in inducing acute lung injury mediated by IL-1 through the oxidative stress by neutrophils. By causing endothelial damage, functional changes of pulmonary surfactant and alveolar type I pneumocyte, oxidative stress disrupts microvascular integrity and alveolar barrier.

• Archives of Pharmacal Research
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• v.20 no.3
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• pp.234-238
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• 1997

CINC-1 is a member of chemokine family with chemotactic and activating properties to neutrophils. CINC-1 induction in IL-$1{\beta}$-stimulated rat fibroblast NRK-49F cells was quantitated by a sensitive ELISA. CINC-1 production was increased up to 135 ng/ml from basal 2-6 ng/ml by stimulation with IL-$1{\beta}$.Steroidal anti-inflammatory drugs including dexamethasone and prednisolone exhibited potent suppressive effects on IL-$1{\beta}$-induced CINC-1 production. Among 39 kinds of natural triterpenoids tested, acacigenin B exhibited the highest suppressive effects with about $10{\mu}M$ to be 50% of inhibition on the CINC-1 induction. The suppressive potency of acacigenin B on IL-$1{\beta}$induced CINC-1 production was about 10-fold less than that of the steroidal anti-inflammatory drugs.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.691-702
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• 2000

Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

• Journal of Ginseng Research
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• v.14 no.3
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• pp.391-398
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• 1990

The intradermal injection of Propionibacterium acnes (ATCC 6919) into the ears of female Sprague-Dawley rats produced a chronic inflammation with the formation of acneiform lesions. Inflammation was characterized by more than four times of ear thickness and 2.8 times of ear weight at day 21. Histologically, massive infiltration of neutrophils, macrophage and lymphocytes, hyperplastic epidermis, comedones containing keratin mass and inflammatory materials were observed. Both ginseng saponin and extract from Korean red ginseng significantly redliced the ear thickness and their effects were similar to that of benzoyl peroxide. Ginseng samples and beneoyl peroxide modified lipid constituents of P. acnesinjected rat ear tissues. Even though no marked histological changes in inflammatory lesions were observed in ginseng-treated ear tissues, Korean red ginseng showed a possibility of reduce in the risk of acne development.