• Journal of Life Science
• /
• v.28 no.2
• /
• pp.207-215
• /
• 2018

Inflammatory response and oxidative stress play critical roles in the development and progression of many human diseases. Therefore, a great deal of attention has been focused on finding functional materials that can control inflammation and oxidative stress simultaneously. The purpose of this study was to investigate the effects of Socheongja and Socheong 2, Korean black seed coat soybean varieties, on the inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our data indicated that the extracts of Socheongja (SCJ) and Socheong 2 (SC2) significantly suppressed LPS-induced production of nitrite oxide (NO) and prostaglandin $E_2$, key pro-inflammatory mediators, by suppressing the expression of inducible NO synthase and cyclooxygenase-2. It was also found that SCJ and SC2 reduced the LPS-induced secretion of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$, which was concomitant with a decrease in the protein levels. In addition, SCJ and SC2 markedly diminished LPS-stimulated intracellular reactive oxygen species accumulation, and effectively enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression. Furthermore, LPS-induced activation of mitogen-activated protein kinases (MAPKs) was abrogated by SCJ and SC2. Taken together, these data suggest that SCJ and SC2 may offer protective roles against LPS-induced inflammatory and oxidative responses in RAW 264.7 macrophages through attenuating MAPKs pathway, and these effects are mediated, at least in part, through activating Nrf2/HO-1 pathway. Given these results, we propose that SCJ and SC2 have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by over-activation of macrophages.

• Journal of Life Science
• /
• v.28 no.12
• /
• pp.1516-1522
• /
• 2018

Atherosclerosis is an obstructive vessel disease mainly caused by chronic arterial inflammation to which the proliferation and migration of vascular smooth muscle cells (VSMCs) is the main pathological response. In the present study, the primary responsible inflammatory cytokine and its signaling pathway was investigated. The proliferation and migration of VSMCs was significantly enhanced by the prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$), while neither was affected by tumor necrosis factor ${\alpha}$. Prostacyclin $I_2$ was seen to enhance the proliferation of VSMCs while simultaneously suppressing their migration. Both prostaglandin $D_2$ and prostaglandin $E_2$ significantly enhanced the migration of VSMCs, however, proliferation was not affected by either of them. The proliferation and migration of VSMCs stimulated by $PGF_{2{\alpha}}$ progressed in a dose-dependent manner; the $EC_{50}$ value of both proliferation and migration was $0.1{\mu}M$. VSMCs highly expressed the phospholipase isoform $C-{\beta}3$ ($PLC-{\beta}3$) while others such as $PLC-{\beta}1$, $PLC-{\beta}2$, and $PLC-{\beta}4$ were not expressed. Inhibition of the PLCs by U73122 completely blocked the $PGF_{2{\alpha}}$-induced migration of VSMCs, and, in addition, silencing $PLC-{\beta}3$ significantly diminished the $PGF_{2{\alpha}}$-induced proliferation and migration of VSMCs. Given these results, we suggest that $PGF_{2{\alpha}}$ plays a crucial role in the proliferation and migration of VSMCs, and activation of $PLC-{\beta}3$ could be involved in their $PGF_{2{\alpha}}$-dependent migration.

• Journal of Life Science
• /
• v.31 no.12
• /
• pp.1110-1119
• /
• 2021

The purpose of this study was to investigate whether the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages could be promoted by particulate matter 2.5 (PM_2.5) stimulation. To this end, the levels of inflammatory parameters, reactive oxygen species (ROS) and inflammation-regulating genes were investigated in RAW 264.7 cells treated with PM_2.5 in the presence or absence of LPS. Our results showed that the production levels of pro-inflammatory mediators (nitric oxide and prostaglandin E₂) and cytokines (interleukin-6 and -1β) were significantly increased by PM_2.5 stimulation in LPS-treated RAW 264.7 cells, which was correlated with increased expression genes involved in their production. In addition, when LPS-treated RAW 264.7 cells were exposed to PM_2.5, nuclear factor-kappaB (NF-κB) expression was further increased in the nucleus, and the expression of inhibitor of NF-κB as well as NF-κB in the cytoplasm was decreased. These results suggest that the co-treatment of PM_2.5 and LPS further increases the activation of the NF-κB signaling pathway compared to each treatment alone, thereby contributing to the promotion of transcriptional activity of inflammatory genes. Furthermore, although the generation of ROS was greatly increased by PM_2.5 in LPS-treated RAW 264.7 cells, the NF-κB inhibitor did not reduce the generation of ROS. In addition, when the generation of ROS was artificially suppressed, the production of inflammatory mediators and the activation of NF-κB were both abolished. Therefore, our results suggest that the increase in the NF-κB-mediated inflammatory response induced by PM_2.5 in LPS-treated RAW 264.7 macrophages was a ROS generation-dependent phenomenon.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.33 no.1 s.60
• /
• pp.53-60
• /
• 2007

(6R)-5,6,7,8-tetrahydrobiopterin ($6-BH_4$) cofactor is essential for various process, and is present in probably every cell or tissue of higher organism. $6-BH_4$ is required lot various enzyme activities, and for less defined functions at the cellular level. And it is well known about the antioxidant effects as a non-protein compound. Recently, scientists proposed another roles for $6-BH_4$ in melanogenesis. $6-BH_4$ is a well known tyrosinase inhibitor. In this study, we found that methyl-$BH_4$ and $6-BH_4$ have antioxidant activities and inhibitory activity for melanin synthesis. These pterin compounds were not toxic in HaCaT and B16F10 cells and showed scavenging activity against DPPH radicals. We also showed that pterin compounds decreased protein levels of tyrosinase and TRP-1. In a clinical test, pterin compounds showed the significant skin whiteining effect after treatment for 3 weeks. Furthermore pterin compounds significantly suppressed the UVB-induced expression of $PGE_2$ and IL-6 genes induced UVB In HaCaT and inhibited UVB-induced melanogenesis in B16F10 cells. These results showed the effect of pterin compounds as a cosmeceutical ingredient.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.32 no.3
• /
• pp.450-457
• /
• 2003

This study was conducted to investigate the effects of high amylose corn starch consumption on plasma, liver and feces lipid profiles and immune responses in male Sprague-Dawley rats. Experimental animals were fed on diets containing the high amylose starch (HAS,0, 125, 250,500 g/kg diet) for 4 weeks. HAS intake did not affect on food intakes and food efficiency ratio. Final body weights were lowered in HA100 group than in control group. HAS intakes dose dependently increased the weights of cecum and excretion of feces per day, and decreased the pH of cecum contents. And HAS intakes significantly decreased the plasma total lipid, triglyceride and total cholesterol levels. But there were not significant differences total lipid, triglyceride and cholesterol concentrations in liver. The absolute and relative weights of thymus and spleen, plasma Is G and $C_3$ concentrations were unaffected by experimental diets. The splenocyte proliferations with low dose Con A (0.1$\mu\textrm{g}$/10 $\mu$L) as lower in HA25 group and HA50 group than in control group. These results demonstrate that high amylose corn starch intakes significantly improve lipid profiles in plasma.

• Tuberculosis and Respiratory Diseases
• /
• v.69 no.6
• /
• pp.456-464
• /
• 2010

Background: Synergistic antitumor effects of the combined chemoimmunotherapy based on dendritic cells have been reported recently. The aim of this study is to search new applicability of gefitinib into the combination treatment through the confirmation of gefitinib effects on the monocyte derived dendritic cells (moDCs); most potent antigen presenting cell (APC). Methods: Immature and mature monocyte-derived dendritic cell (im, mMoDC)s were generated from peripheral blood monocyte (PBMC) in Opti-MEM culture medium supplemented with IL-4, GM-CSF and cocktail, consisting of TNF-${\alpha}$ (10 ng/mL), IL-$1{\beta}$ (10 ng/mL), IL-6 (1,000 U/mL) and $PGE_2$ ($1{\mu}/mL$). Various concentrations of gefitinib also added on day 6 to see the influence on immature and mature MoDCs. Immunophenotyping of DCs under the gefitinib was performed by using monoclonal antibodies (CD14, CD80, CD83, CD86, HLA-ABC, HLA-DR). Supernatant IL-12 production and apoptosis of DCs was evaluated. And MLR assay with $[^3H]$-thymidine uptake assay was done. Results: Expression of CD83, MHC I were decreased in mMoDCs and MHC I was decreased in imMoDCs under gefitinib. IL-12 production from mMoDCs was decreased under $10{\mu}M$ of gefitinib sinificantly. Differences of T cell proliferation capacity were not observed in each concentration of geftinib. Conclusion: In spite of decreased expressions of some dendritic cell surface molecules and IL-12 production under $10{\mu}M$ of gefitinib, significant negative influences of gefitinib in antigen presenting capacity and T cell stimulation were not observed.

• Korean Journal of Plant Resources
• /
• v.32 no.4
• /
• pp.282-289
• /
• 2019

Gastritis is an inflammatory disease involving the stomach and is caused by several factors, including stress, non-steroidal anti-inflammatory drugs such as aspirin, liquor, and Helicobacter pylori. In Korea, Leonurus japonicus Houttuyn (LJW) has been used as traditional medicine for vaginal bleeding, hematuria, and bruise. Previous studies have reported that LJW exhibited hepatoprotective, cardioprotective, and anti-hyperlipidemic effect. However, the effect of the water extract of LJW on gastritis was not elucidated. Thus, we evaluated the anti-gastric effect and genotoxicity of LJW. LJW effectively prevented the degeneration of surface mucous cells and glandular epithelial cells and vascular congestion induced by HCl/EtOH. Micronucleus assay indicated that the rate of micronucleated polychromatic erythrocytes/polychromatic erythrocytes was not significantly different compared that of the control. Further experiments are required to determine the role of LJW in the gastric injury process such as cyclooxygenase signaling pathway and the secretion of mucus in the stomach.

• Journal of Life Science
• /
• v.21 no.6
• /
• pp.796-804
• /
• 2011

Microglia are central nervous system (CNS)-resident professional macrophages that function as the principal immune cells responding to pathological stimulations in the CNS. Activation of microglia, induced by various pathogens, protects neurons and maintains homeostasis in the CNS, but severe activation causes inflammatory responses secreting various neurotoxic molecules such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines. Allium fistulosum, a member of the onion family, is mainly cultivated for consumption, as well as medicinal use in Oriental medicine. It has been reported that A. fistulosum has various biological effects such as anti-oxidant, anti-platelet aggregation, anti-fungus and anti-cholesterol synthesis, however there has been no research about the anti-inflammatory effects of A. fistulosum extracts. In this study, it was undertaken to explore the functions of A. fistulosum as a suppressor of neuronal inflammation by using BV2 microglia cells. As a result, it was found that four kinds of extracts of A. fistulosum effectively reduced the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels, and also attenuated pro-inflammatory cytokines such as tumor necrosis alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6) at the mRNA level in BV2 stimulated by lipopolysaccharide (LPS). In addition, the extracts of A. fistulosum attenuated the release of NO markedly, as well as resulting in slight decreases of TNF-${\alpha}$ and IL-6 production, the effects of which were most significant when treated with ethyl alcohol extract from the whole A. fistulosum. In conclusion, the data indicated that the anti-inflammatory actions of A. fistulosum against BV2 microglia cells is through the down-regulation of iNOS, COX2 and pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-6, and these effects are expected to help in the protection of nerve tissues by suppressions of neuronal inflammation in various neurodegenerative diseases.

• Journal of Life Science
• /
• v.27 no.9
• /
• pp.1020-1030
• /
• 2017

Epidemiology studies have reported a reduced incidence of colon cancer among populations that consume a large quantity of ${\omega}3-polyunsaturated$ fatty acids (${\omega}3-PUFAs$) of marine origin. Herein, we demonstrated a mechanism of anticancer action of ${\omega}3-PUFAs$, showing that they suppressed invasion and tumorigenicity in colon cancer cells. Docosahexaenoic acids (DHA) inhibited the cell growth of HT29 cells. This action likely involved apoptosis, given that the DHA treatment increased the cleaved form of PARP and sub G1 cells. Moreover, the invasiveness of HT29 cells was inhibited following DHA treatment, whereas arachidonic acid (AA) had no effect. The levels of Matrix-metalloproteinase-9 (MMP-9) and MMP-2 mRNA decreased after DHA pretreatment. DHA treatment inhibited MMP-9 and MMP-2 promoter activities and reduced VEGF promoter activity. DHA pretreatment also inhibited the activities of prostaglandin-2 (PGE2)-induced MMPs and the VEGF promoter. Cyclooxygenase-2 (COX-2) overexpression increased the activity of MMPs and that of the Vascular endotherial growth factor (VEGF) promoter in HT29 cells, and DHA inhibited NF-kB and COX-2 promoter reporter activities. As shown by in vivo experiments, when mouse colon cancer cells (MCA38) were implanted into Fat-1 and wild-type mice, both the tumoral size and volume were dramatically inhibited in Fat-1 transgenic mice. Furthermore, TUNEL-positive cells increased in tumors from Fat-1 mice compared with wild mice. In immunohistochemistry, the intensity of CD31 in Fat-1 tumors was weaker. These findings suggest that ${\omega}3-PUFAs$ may inhibit tumorigenicity and angiogenesis as well as cancer cell invasion by suppression of COX-2, MMPs and VEGF via the reduction of NF-kB in colon cancer.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.39 no.5
• /
• pp.684-691
• /
• 2010

The present study was conducted to evaluate the effect of resistant starch (RS) on the large bowel function and plasma lipids in rats with constipation induced by Loperamide. Animals were divided into six groups: normal control-5% cellulose, constipation-5% cellulose, constipation-5% pectin, constipation-5% RS-type 2 (RS2), constipation-8% RS2 and constipation-5% RS type 3 (RS3) groups, and fed experimental diets for five weeks. The results from RS groups were compared with those from other dietary fiber groups. The groups supplemented with RS3 or high level of RS2 showed significantly increased counts of bifidobacteria in the cecum than the other groups. The production of total short chain fatty acids in the cecal contents was significantly high in pectin, RS3 and high RS2 groups. The pH in the cecal contents of the RS supplemented groups was significantly decreased compared with the cellulose supplemented groups. The production of prostaglandin E2 in the colon mucus of the RS groups was higher than the normal group; however, it was significantly decreased compared to the cellulose or pectin supplemented constipated groups. The thickness of the mucus layer and the production of mucus from epithelial cells were significantly increased in RS3 group compared to the constipated cellulose group. Supplementation of resistant starch significantly elevated the ratio of HDL-cholesterol to total cholesterol and significantly lowered plasma atherogenic index compared with cellulose or pectin supplementation in constipated rats. The results of the present study demonstrated that resistant starch supplementation may help in improving the large bowel environment by stimulation of bifidobacterial proliferation, reduction of pH and inflammation factor and by increased production of mucus. It has also been found that an additional health benefit is improvement in lipid levels of serum.