• Journal of Physiology & Pathology in Korean Medicine
• /
• v.23 no.3
• /
• pp.599-607
• /
• 2009

Prunellae Spica is the spike or whole plant of Prunella vulgaris Linne, which has been used for clearing heat from the liver, brightening the eyes and treating headache in traditional oriental medicines. This study was conducted to evaluate the inhibitory effects of the aqueous extract of Prunellae Spica (PSE; PS extract) on the production of NO and PGE2 in LPS-activated Raw 264.7 cells. Cell viability was determined by MTT assay, and all three doses of PS extract (0.03, 0.1 and 0.3 mg/ml) had no significant cytotoxicity during the entire experimental period. The cells were treated with 1 ${\mu}g/ml$ of LPS 1 h before adding PS extract, and increased NO and PGE2 production were detected in LPS-activated cells compared to control. However, these increases were dose-dependently attenuated by treatment with PS extract. The inhibition of NO by PS extract was due to the suppression of iNOS expression via inhibition of $NF{\kappa}B$ nuclear translocation and proteolytic degradation of $I{\kappa}B{\alpha}$. The decreased level of PGE2 was derived from inhibition of COX-2 activity, but expression of COX-2 protein was not affected by PS extract. Moreover, PS extract reduced the elevated production of IL-${\beta}$ and IL-6 by LPS. These results demonstrate that PS extract has inhibitory effects on the production of NO and PGE2 as a consequence of the reduction of proinflammatory cytokines, especially IL-${\beta}$ and IL-6 in LPS-activated Raw 264.7 cells.

• Clinical and Experimental Pediatrics
• /
• v.51 no.6
• /
• pp.597-603
• /
• 2008

Purpose : Obesity is associated with insulin resistance. Insulin resistance and the presence of pro-inflammatory mediators are thought to cause a state of vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation. These chronic inflammatory responses, which are characterized by abnormal cytokine production, lead to activation of a pro-inflammatory signaling pathway. Leptin is an important mediator of inflammatory processes and immune-mediated diseases. The purpose of this study was to investigate the relationship between leptin and various cytokines associated with obesity in adolescents. Methods : Sixty-six obese adolescents (between 16-17 years of age, obesity index >130%) and 26 normal controls were included in this study. Obesity index and body mass index (BMI) were calculated. Serum lipid profile, AST and ALT were tested after 10 hours of fasting. Tumor necrosis factor alpha (TNF-${\alpha}$) and Interleukin-6 (IL-6) levels were measured by ELISA. Insulin, adiponectin, and leptin levels were estimated by radioimmunoassay. Results : Leptin was significantly higher in the obese adolescents compared to the control adolescents ($12.0{\pm}6.8ng/mL$ vs $6.3{\pm}1.0ng/mL$). TNF-${\alpha}$, IL-6, and insulin were significantly higher in the obese adolescents. Adiponectin was significantly lower in the obese group than the control group ($3.3{\pm}1.9{\mu}g/mL$ vs $5.0{\pm}1.4{\mu}g/mL$). Leptin had positive correlations with obesity index, BMI, and IL-6. Conclusion : In obese adolescents, leptin, TNF-${\alpha}$, IL-6, and insulin might be important mediators of obesity. Further clinical research is necessary to ascertain leptin as a predictor of cardiovascular diseases and to develop a guideline for clinical intervention.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.42 no.10
• /
• pp.1552-1559
• /
• 2013

Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• Microbiology and Biotechnology Letters
• /
• v.43 no.1
• /
• pp.45-55
• /
• 2015

This study was carried out to demonstrate the anti-inflammatory effect of tuna oil (TO) using LPS-induced inflammation responses and mouse models. First, nitric oxide (NO) and pro-inflammatory cytokines levels were suppressed up to 50% with increasing concentrations of TO without causing any cytotoxicity. Also, the expression of a variety of proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB), was suppressed in a dosedependent manner by treatment with TO. Furthermore, TO also inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 protein kinase (p38). Moreover, in in vivo testing the formation of ear edema was reduced at the highest dose tested compared to that in the control, and a reduction of ear thickness and the number of mast cells was observed in histological analysis. In acute toxicity test, no mortalities occurred in mice administrated 5,000 mg/kg body weight of TO over a two-week observation period. Our results suggest that TO has a considerable anti-inflammatory property through the suppression of inflammatory mediator productions and that it could prove to be useful as a potential anti-inflammatory therapeutic material.

• The Korea Journal of Herbology
• /
• v.35 no.4
• /
• pp.51-60
• /
• 2020

Objective : The objective of this study was to demonstrate the effect of Persicae Semen (PS) in DNCB-induced atopic dermatitis mouse and HaCaT cell. Methods : The BALB/c mice were divided into four groups. To develop atopic dermatitis, 200 ㎕ of 1 and 0.5% DNCB solution was put on the back of mice in the Control group, the PS-Low group and the PS-High group once a day. After application of DNCB, 200 ㎕ of the PS extract was also treated. The Normal group was given PBS. The mice dorsal skin was stained with Masson's trichrome, H&E, and toluidine blue to evaluate the thickness of the epidermis and dermis, infiltration of eosinophils and mast cells respectively. ELISA was applied to measure the serum level of IgE and IL-6. Toxicity of PS was measured by MTS assay in HaCaT cell. To investigate the effects of PS on HaCaT cells, cells were pre-treated with PS for 1h, and then stimulated with TNF-α and IFN-γ. After 24 hours, the expression of TARC was analyzed using RT-PCR. Results : PS not only significantly diminished the thickness of the epidermis and dermis, but also reduced the infiltration of eosinophil and mast cell in skin lesion. PS also reduced the serum IgE and IL-6 level which plated important roles in the atopic dermatitis. The expression of TARC was decreased significantly in TNF-α/IFN-γ stimulated HaCaT cell. Conclusion : These results suggest that PS may be effective in alleviating the atopic dermatitis induced by DNCB and inflammation by TNF-α/IFN-γ.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.40 no.4
• /
• pp.486-492
• /
• 2011

This study was designed to evaluate the effect of hot water extract (ESW) and 70% ethanol extract (ESE) from Euphorbia supina Rafin on LPS-stimulated inflammatory response in RAW 264.7 macrophages. Upon investigation at concentrations up to $1000\;{\mu}g$/mL, ESW and ESE did not have any cytotoxic effects on RAW 264.7 macrophages. ESW induced inhibition of 21.6%~54.8% of nitric oxide (NO) production at 100~1000${\mu}g$/mL, and $PGE_2$ production was inhibited up to 25.7%~38.2% at 250~1000${\mu}g$/mL, proportional to the ESW concentrations. ESW induced inhibition of 66.1% and 54.3% of IL-6 production at 250 and $1000\;{\mu}g$/mL, respectively. ESE (100~1000${\mu}g$/mL) induced inhibition of 38.3%~77.5% of NO, 40%~94.7% of $PGE_2$, and 43.9%~89.4% of IL-6 production, proportional to the ESE concentrations. Only 44.1% of IL-10 production was inhibited at a concentration of $500\;{\mu}g$/mL. ESE induced an increase in TNF-${\alpha}$ production at a concentration of 100 and $250\;{\mu}g$/mL, whereas at high concentrations (500 and $1000\;{\mu}g$/mL), ESE induced inhibition of 19.2% and 92.4% of TNF-${\alpha}$ production, respectively. In conclusion, concentrations of more than $500\;{\mu}g$/mL ESE demonstrated effective immune-modulating activity through inhibition of NO, $PGE_2$, IL-6, IL-10, or TNF-${\alpha}$ production, as it relates to the macrophage's immuno-activity; therefore, ESE has potential as a good candidate substance for reduction of inflammatory responses.

• Tuberculosis and Respiratory Diseases
• /
• v.62 no.4
• /
• pp.299-307
• /
• 2007

Background: High mobility group box 1 (HMGB1) is a novel, late mediator of inflammation. This study compared the pro-inflammatory effects of LPS and HMGB1. The transcriptional factors that play an important role in mediating the HMGB1-induced stimulation of IL-8 were also evaluated. Methods: RAW264.7 cells were stimulated with either LPS (100 ng/ml) or HMGB1 (500 ng/ml). The $TNF-{\alpha}$, MIP-2 and $IL-1{\beta}$ levels in the supernatant were evaluated by ELISA at 0, 2, 4, 8, 12 and 24h after stimulation. An acute lung injury was induced by an injection of LPS (5 mg/kg) or HMGB1 (2.5 mg/kg) into the peritoneum of the Balb/c mice. The lung cytokines and MPO activity were measured at 4h (for LPS) or 24h (for HMGB1) after the injection. The transcriptional factor binding sites for NF-IL6, $NF-{\kappa}B$ and AP-1 in the IL-8 promoter region were artificially mutated. Each mutant was ligated with pIL-6luc and transfected into the RAW264.7 cells. One hour after stimulation with HMGB1 (500 ng/ml), the cell lysate was analyzed for the luciferase activity. Results: The expression of MIP-2, which peaked at 8h with LPS stimulation, increased sequentially until 24h after HMGB1 stimulation. An intraperitoneal injection of HMGB1, which induced a minimal increased in $IL-1{\beta}$ expression, provoked the accumulation of neutrophils the lung. A mutation of AP-1 as well as $NF-{\kappa}B$ in the IL-8 promoter region resulted in a lower luciferase activity after HMGB1 stimulation. Conclusion: The proinflammatory effects of HMGB1, particularly on IL-8, are mediated by both $NF-{\kappa}B$ and AP-1.