• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.1
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• pp.1-24
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• 2013

Objectives: The object of this study was to observe the protective effect of Gamijipaesan aqueous extracts(GJS), which has been traditionally used in Korean medicine in obstetrics & gynecological fields as anti-infectious and anti-inflammatory agents, against mastitis induced by Staphylococcus aureus infection in a rat model through antibacterial, antiinflammatory, immunomodulatory, and anti-oxidant effects. Methods: Antibacterial activities of GJS against S. aureus were detected using standard agar microdilution methods, with the effects on the bacterial invasion and intracellular killing of individual test materials in human mammary gland carcinoma cell(MCF-7) and murine macrophages(Raw 264.7) at MIC1/2, MIC and MIC2 concentration levels. In addition, the effects on the cell viability, nitric oxide(NO), tumor necrosis factor(TNF)-${\alpha}$ and interleukin (IL)-6 productions of LPS activated Raw 264.7 cells. The changes on the mammary tissue viable bacterial numbers, myeloperoxidae(MPO), inducible nitric oxide synthetase(iNOS), TNF-${\alpha}$ and IL-6 contents were observed in the S. aureus in vivo intramammary infectious rat model. The anti-bacterial and anti-inflammatory effects were compared with ciprofloxacin and piroxicam, respectively in the present study. Results: MIC of GJS and ciprofloxacin against S. aureus were detected as $0.860{\pm}0.428$ (0.391-1.563) mg/ml and $0.371{\pm}0.262$(0.098-0.782) ${\mu}g/ml$, respectively. In addition, GJS and ciprofloxacin were also showed marked dosage-dependent inhibition of the both bacterial invasion and intracellular killing assays using MCF-7 and Raw 264.7 cells at MIC1/2, MIC and $MIC{\times}2$ concentrations, respectively. $ED_{50}$ against LPS-induced cell viabilities and NO, TNF-${\alpha}$ and IL-6 releases of GJS were detected as 0.72, 0.04, 0.08 and 0.11 mg/ml, and as 19.04, 4.18, 5.37 and 4.27 ${\mu}g/ml$ in piroxicam, respectively. 250 and 500 mg/kg of GJS also inhibit the intramammary bacterial growth, MPO, iNOS, TNF-${\alpha}$ and IL-6 contents in S. aureus in vivo intramammary infected rats, respectively. GJS 500 mg/kg showed quite similar antibacterial and anti-infectious effects as compared with ciprofloxacin 40 mg/kg and also showed similar anti-inflammatory effects as piroxicam 10 mg/kg, in S. aureus in vivo intramammary infectious models. Conclusions: The results obtained in this study suggest that over 250 mg/kg of GJS showed favorable anti-infectious effects against S. aureus infection in a rat model through their antibacterial, anti-inflammatory, immunomodulatory and anti-oxidant effects and therefore expected that GJS can be used as alternative therapies, having both anti-inflammatory and anti-infectious activities. However, more detail mechanism studies should be conducted in future with the efficacy tests of individual herbal composition of GJS and the screening of the biological active compounds in individual herbs. In the present study, GJS 500 mg/kg showed quite similar anti-infectious effects were detected as compared with ciprofloxacin 40 mg/kg treated rats, and also GJS shows quite similar anti-inflammatory effects as compared with piroxicam 10 mg/kg in S. aureus in vivo intramammary infectious rats, but ciprofloxacin did not showed any anti-inflammatory effects, and piroxicam did not showed anti-infectious effects in this study.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.522-534
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• 1995

Background: In the pathogenesis of acute lung injury induced by lipopolysaccharide(LPS), oxygen radiclls are known to be involved in one part. Superoxide dismutase(SOD) protects oxygen radical-induced tissue damage by dismutating superoxide to hydrogen peroxide. In eukaryotic cells, two forms of SOD exist intracellularly as a cytosolic, dimeric copper/zinc-containing SOD(CuZnSOD) and a mitochondrial, tetrameric manganese-containing SOD(MnSOD). But there has been little information about SOD gene expression and its regulation in pulmonary alveolar macrophages(PAMs). The objective of this study is to evaluate the SOD gene expression induced by LPS and its regulation in PAMs of rat. Method: In Sprague-Dawley rats, PAMs obtained by broncholaveolar lavage were purified by adherence to plastic plate. To study the effect of LPS on the SOD gene expression of PAMs, they were stimulated with different doses of LPS($0.01{\mu}g/ml{\sim}10{\mu}g/ml$) and for different intervals(0, 2, 4, 8, 24hrs). Also for evaluating the level of SOD gene regulation actinomycin D(AD) or cycloheximide(CHX) were added respectively. To assess whether LPS altered SOD mRNA stability, the rate of mRNA decay was determined in control group and LPS-treated group. Total cellular RNA extraction by guanidinium thiocyanate/phenolfchlorofonn method and Northern blot analysis by using a $^{32}P$-labelled rat MnSOD and CuZnSOD cDNAs were performed. Results: The expression of mRNA in MnSOD increased dose-dependently, but not in CuZnSOD. MnSOD mRNA expression peaked at 8 hours after LPS treatment. Upregulation of MnSOD mRNA expression induced by LPS was suppressed by adding AD or CHX respectively. MnSOD mRNA stability was not altered by LPS. Conclusion: These findings show that PAMs of rat could be an important source of SOD in response to LPS, and suggest that their MnSOD mRNA expression may be regulated transcriptionally and require de novo protein synthesis without affecting mRNA stability.

• Journal of Food Hygiene and Safety
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• v.28 no.4
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• pp.360-366
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• 2013

The objective of this study is to investigate the effect of multivitamin on macrophage activity in Raw 264.7 cell and repeated oral dose toxicity in Sprague-Dawely rat of multivitamin. Raw 264.7 cells were treated with 50 and $100{\mu}g/mL$ multivitamin for 24 h. To measure the activity of macrophages, NO and TNF-${\alpha}$ assays were performed in Raw 264.7 cells. Treatment with 50 and $100{\mu}g/mL$ multivitamin for 24 h significantly increased production of NO and TNF-${\alpha}$ compared with control groups, indicating activation of macrophages. The female rats were treated with multivitamin of control group, low group (0.24 g/kg), medium group (1 g/kg) and high group (2 g/kg) intragastrically for 4 weeks, respectively. We examined the body weight, the feed intake, the clinical signs and serum biochemical analysis. We also observed the histopathological changes of liver, ovary, brain, adrenal gland, spleen, kidney, heart and lung in rats. No significant differences in body weights, feed intake, biochemical analysis and histopathological observations between control and multivitamin treatment group were found. In conclusion, multivitamin is physiologically safe and improve macrophage activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.206-213
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• 2009

Sophora flavescens, as a traditional herbal medicine, has been used to treat with a variety of disesases, In previous reports, S. flavescens and sophoraflavanone G (a prenylated flavonoid from S. flavescens) inhibited cytokines productions in LPS-induced Raw 264.7 macrophages cells and BV2 microglial cells. We examined on the anti-allergic effect of S. flavescens on the PMA plus A23187-induced rat leukemia (RBL-2H3) cells. S. flavescens inhibited the release of $\beta$-hexosaminidase and productions and expressions of tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-4 and cyclooxygenase (COX)-2 in a dose-dependent manner on stimulated RBL-2H3 cells, however, S. flavescens not affect cell viability. The protein expression level of nuclear factor (NF)-${\kappa}B$ (p65) was decreased in the nucleus and suppressed the degradation of inhibitory protein $I{\kappa}B-{\alpha}$ protein, the activation of extracellular signal-regulated kinases (ERK) mitogen-activated protein kinase (MAPK) by S. flavescens. These results suggest that S. flavescens could be involved anti-allergic effect by control of $NF-{\kappa}B$ (p65) translocation into the nucleus through inhibition of $I{\kappa}B-{\alpha}$ degradation and suppression of pro-inflammatory cytokines expression.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.4
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• pp.497-505
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• 2015

Traditional herbs, such as Lonicera japonica, Arctii Fructus, and Scutellariae Radix have been used as traditional drug due to their anti-inflammatory and anti-oxidant activities. The aim of this study was to investigate the anti-inflammatory effects of extract mixture (YG-1) in a model of lipopolysaccharide (LPS)-induced acute inflammation in both macrophage (RAW 264.7) cells and Sprague-Dawley rats. YG-1 did not show specific cellular toxicity in RAW 264.7 cells until a concentration of $100{\mu}g/mL$. YG-1 reduced various markers related to inflammation such as IL-$1{\beta}$, COX-2, and iNOS caused by LPS in RAW 264.7 cells. Consistent with these results, YG-1 exerted significant anti-inflammatory effects in an acute inflammation rat model. Acute fever and high concentration of IL-$1{\beta}$ in serum induced by LPS were significantly reduced by YG-1. These results were similar to flubiprofen, a commercial anti-inflammatory and anti-febrile drug. Therefore, these results indicate that YG-1 has beneficial effects on LPS-induced acute inflammation and suggest that YG-1 can serve as an effective anti-inflammatory and anti-febrile drug.

• Toxicological Research
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• v.21 no.2
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• pp.141-150
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• 2005

1,3-Dichloro-2-propanol (1,3-DCP) is known as chloride chemicals and causes severe hepatotoxic agent. The Ito cells and Kupffer's cells of the liver in the 5 old F344 Rats were exposed to 1,3-DCP gas chamber for 6 hours/ a day, 5 days/ a week, and 13 weeks, in the 0, 5, 20, 80 ppm, respectively. After then the body weights, liver weights, and relative liver weight to body weight were measured, and the hepatic tissues were prepared by the routine and Immunostain method, and observed by the LM, and EM. In the results, there were severe body weight decrease (p<0.05) in the 80 ppm of the male and female rats. The relative liver weights to the body weight were increased relate with exposed 1,3-DCP concentration (P<0.001). Inflammatory cells, infiltration was observed at the perivascular area in the 20 ppm exposed group, and bilirubin pigment infiltration, bile duct hyperplasia, inflammation hepatocytic necrosis, fibrosis were observed in the 80 ppm exposure group. In the 80 ppm exposure group, disarrangement of the endothelial cells, erythrocytes and hepatic cell fragment in the Disse space and numerous migration macrophages were observed in the necrotic area by EM observation. In the immunostained hepatic tissues positive stained ED1 cells were extremely increased (P<0.05) in central vein area, but ED2 was weakly positive immunostained in the 80 ppm exposed group. Immunostained desmin was observed in the Ito cell. It was no difference in the low and medium exposed group but it was typical increase in the necrotic area. In conclusion, These results suggest that NOAEL of 1,3-DCP may be 5 ppm in rats and the Immunostained of desmin, ED1 and ED2 positive cells activated in the inflammatory liver were related to the exposure volume and density. The increase of the Ito cells were related to the severe phagocytosis of the Kupffer's cells.

• Journal of Mushroom
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• v.18 no.3
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• pp.260-267
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• 2020

Phellinus baumii, a white-rot fungus, has been used for centuries as folk medicine in China, Japan, and Korea. This study aimed to evaluate the in vitro anti-diabetic, and anti-cholinesterase, and in vivo anti-inflammatory effects of the fruiting bodies of P. baumii. The methanol (ME) and hot water (HE) extracts (2.0 mg/mL) of P. baumii fruiting bodies suppressed α-amylase activity, exactly 61.33%, and 65.00%, respectively; of note, acarbose, the positive control, inhibited 93.33% of the α-amylase activity. Moreover, the ME and HE (2.0 mg/mL) inhibited 89.67% and 91.00%, respectively, of the activity of α-glucosidase activity, whereas the same concentration of acarbose suppressed 84.67% of the α-glucosidase activity. The ME and HE (1.0 mg/mL) also inhibited 96.05% and 94.58%, respectively, of the acetylcholinesterase (AChE) activity; galanthamine, the positive control, led to an inhibition of 81.12%. The butyrylcholinesterase (BChE) activity was also inhibited by ME and HE (1.0 mg/mL; 91.05% and 82.27%, respectively); of note, the same concentration of galanthamine suppressed 81.12% of the BChE activity. The production of NO in LPS-induced RAW 264.7 macrophages was significantly suppressed by both ME and HE treatments. Importantly, the carrageenan-activated rat hind-paw edema was significantly reduced 2-6 h after ME administration (50 mg/mL). Taken together, the results suggest that the fruiting bodies of P. baumii have α-amylase, α-glucosidase, α-cholinesterase, and anti-inflammatory activities, and, therefore, may be good natural sources for the promotion of human health.

• Journal of Environmental Health Sciences
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• v.39 no.1
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• pp.48-55
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• 2013

Objective: The use of nanoparticle products is expected to present a potential harmful effect on consumers. Also, the lack of information regarding inhaled nanoparticles may pose a serious problem. In this study, we addressed this issue by studying pulmonary toxicity after nasal instillation of Al-NPs in SD rats. Methods: The animals were exposed to Al-NPs at 1 mg/kg body weight (low dose), 20 mg/kg body weight (medium dose) and 40 mg/kg body weight (high dose). To determine pulmonary toxicity, bronchoalveolar lavage (ts.AnBAL) fluid analysis and histopathological examination were conducted in rats. In addition, cell viability was investigated at 24 hours after the treatment with Al-NPs. Results: BAL fluid analysis showed that total cells (TC) count and total protein (TP) concentrations increased significantly in all treatment groups, approximately two to three times. Also, lactate dehydrogenase (LDH) and cytokines such as TNF-alpha and IL-6 dose-dependently increased following nasal instillation of Al-NPs. However, polymorphonuclear leukocytes (PMNs) levels showed no significant changes in a dose dependant manner in BAL fluid. In the cytotoxicity analysis, the treatment of Al-NPs significantly and dose-dependently induced cell viability loss (20 to 30%) and damage of cell membrane (5 to 10%) in rat normal lung epithelial cells (L2). Conclusions: Our results suggest that inhaled Al-NPs in the lungs may be removed quickly by alveolar macrophages with minimal inflammatory reaction, but Al-NPs have the potential to affect lung permeability. Therefore, extensive toxicity evaluations of Al-NPs are required prior to their practical application as consumer products.

• Tuberculosis and Respiratory Diseases
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• v.39 no.2
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• pp.131-140
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• 1992

In order to investigate the changes of hydroxyproline amount and pathologic finding in rat lung which were instilled the natural coal and free silica dust intratracheally, the subjects were divided into two groups as follows. The control group was only administered intratracheally 0.5 ml of normal saline, and the experimental groups were instilled at once the turbid solution containing 10 mg, 30 mg and 50 mg of natural coal and free silica dust each, subjects were sacrified at the 3rd and the 20th week each after the experiment. Hydroxyproline amount in the right upper lung was measured by Woessner method and HPLC (modified Dunphy) method, and the pathlogic finding of lung tissue were observed for hematoxylin-eosin staining, Bielschowski method and Masson's trichrome method. The results were as follows. 1) The wet lung weights of all experimental groups excluding in the groups instilled 10 mg and 30 mg of natural coal dust at 3rd week, were significantly increased (p<0.05) compared with control group. The weight in each free silica group was markedly increased (p<0.05) at 20th week compared with the same dose of natural coal dust group, while the weight in the same dose group of free silica dust was increased significantly at 20th week compared with at 3rd week. 2) The amount of hydroxyproline were significantly increased (p<0.05) in the natural coal and free silica groups at 20th week compared with the control groups, and in each experimental group instilled the same kind and dose of dust, its amount was markedly increased (p<0.05) at 20th week compared with at 3rd week. And also the hydroxyproline in 30 mg and 50 mg free silica groups increased markedly (p<0.05) at 20th week compared with the natural coal dust of the same dose. 3) The polymorphonuclear leukocytes, fibroblasts and macrophages in interstitium and alveolar space showed the increasing tendency in the free silica group more markedly than in the natural coal dust group. The exudate in alveolar space at 3rd week was disappeared at 20th week, and pneumoconiotic nodules observed microscopically in all experimental groups at 20th week, while the nodules apeared already at 3rd week in the 30 mg and 50 mg free silica dust groups. The significant increase of Hydroxyproline content in lung tissue and pneumoconiotic nodule formation in experimental groups found in this study indicate that the observation period, dust amount and kind of dust is important factors associated with pneumoconiosis. And these findings were generally more severe in free silica dust groups than in natural coal groups.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.223-235
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• 1993

Background: Superoxide anion which was produced by macrophage and neutrophil has a defensive role to kill invasive microorganisms and also an injurious role to produce self lung damage. Production of oxygen free radicals including superoxide is a main mechanism of acute lung injury caused by bacterial endotoxin. Endotoxin is known to activate alveolar macrophage to produce increased oxygen free radicals after the stimulation with various biological materials (priming effect). Calcium is a very important intracellular messenger in that cellular process of superoxide production. Method: This experiment was performed to elucidate the effects of endotoxin and calcium on superoxide production by phorbol myristate acetate-stimulated alveolar macrophage and the effect of verapamil on priming effect of endotoxin. Results: 1) Preincubation of macrophages with endotoxin (E. coli 055-B5) primed the cells to respond with increased superoxide production after the stimulation with PMA. Priming with endotoxin ($10^{-1}$ug/ml) produced a maximal enhancement of superoxide production (43%). 2) Verapamil could inhibit the superoxide production by PMA stimulated macrophage regardless of the presence of extracellular calcium. This means that the inhibitory effect of verapamil is caused by a mechanism independent of blocking calcium influx. 3) Verapamil could inhibit the priming effect of endotoxin on alveolar macrophage (from 30% increment to 13% increment) and could inhibit the superoxide production by PMA-stimulated macrophage preincubated with endotoxin. Conclusion: We concluded that verapamil could inhibit the superoxide production by PMA-stimulated rat alveolar macrophage and also inhibit the priming effect of endotoxin on alveolar macrophage. These inhibitory effects of verapamil could be one of the mechanisms of verapamil effects on endotoxin induced lung injury.