• Journal of Nutrition and Health
• /
• v.51 no.3
• /
• pp.208-214
• /
• 2018

Purpose: Platycodon grandiflorum (a domestic diploid variety, DV-PG) has been used as a food and component of various traditional oriental medicines. Although DV-PG is known to have an anti-allergic effect, little is known about the beneficial health effects of the tetraploid 'Etteum' variety in the Platycodon grandiflorum (TV-PG), which is a recently developed variety. In this study, we investigated the effect of TV-PG on the rat basophilic leukemia mast cell (RBL-2H3)-mediated allergic response. Methods: To examine the effects of TV-PG on the allergic response, RBL-2H3 cells were sensitized with dinitropheny (DNP)-immunoglobin E, treated with various concentrations of TV-PG, and challenged with DNP-human serum albumin. We estimated cell granulation by measuring the release of ${\beta}$-hexosaminidase and production of inflammatory mediators by ELISA. Results: TV-PG had no effect on the proliferation or cytotoxicity of RBL-2H3 cells within the concentration range of 0 to $200{\mu}g/mL$. TV-PG inhibited degranulation of RBL-2H3 cells by antigen stimulation in a dose-dependent manner. TV-PG also suppressed the production of inflammatory cytokines and mediators such as interleukin-4, tumor necrosis $factor-{\alpha}$, prostagladin E2, and leukotriene B4 in RBL-2H3 cells by antigen stimulation. Conclusion: These results indicate that TV-PG exhibits anti-allergic activity via inhibition of degranulation as well as suppression of inflammatory mediators and cytokine release. These findings suggest that TV-PG may have potential as a preventive and therapeutic agent for the treatment of various allergic diseases.

• Nutrition Research and Practice
• /
• v.11 no.1
• /
• pp.43-50
• /
• 2017

BACKGROUND/OBJECTIVES: The present study investigated the hypothesis that a highly pure linear ${\beta}$-1,3-glucan produced by Agrobacterium sp. R259 enhances human natural killer (NK) cell activity and suppresses pro-inflammatory cytokines. SUBJECTS/METHODS: In an eight-week, double-blind, randomized, placebo-controlled clinical trial, 83 healthy adults with white blood cell counts of $4,000-8,000cells/{\mu}L$ were participated and randomly assigned to take two capsules per day containing either 350 mg ${\beta}$-1,3-glucan or placebo. Six participants withdrew their study consent or were excluded due to NK cell activity levels outside the normal range. NK cell activity and serum levels of immunoglobulin G (IgG) and cytokines, such as interferon (IFN)-${\gamma}$, interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-${\alpha}$ were measured. RESULTS: NK cell activity and the serum levels of IL-10 were significantly higher from baseline to week 8 in the ${\beta}$-glucan group compared with the placebo group (P = 0.048, P = 0.029). Consumption of ${\beta}$-1,3-glucan also significantly increased NK cell activity compared with placebo after adjusting for smoking and stress status (P = 0.009). In particular, the effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants with severe stress than in those experiencing mild stress. However, the administration ${\beta}$-1,3-glucan did not significantly modulate the levels of IFN-${\gamma}$, IL-2, IL-4, IL-6, IL-12, TNF-${\alpha}$ and IgG compared with the placebo. CONCLUSION: The results showed that supplementation with bacterial ${\beta}$-1,3-glucan significantly increased NK cell activity without causing any adverse effects. Additionally, the beneficial effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants experiencing severe stress.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.5
• /
• pp.531-546
• /
• 2017

Activation of Toll-like receptor-4 (TLR-4) in articular chondrocytes increases the catabolic compartment and leads to matrix degradation during the development of osteoarthritis. In this study, we determined the proteomic and genomic alterations in human chondrocytes during lipopolysaccharide (LPS)-induced inflammation to elucidate the underlying mechanisms and consequences of TLR-4 activation. Human chondrocytes were cultured with LPS for 12, 24, and 36 h to induce TLR-4 activation. The TLR-4-induced inflammatory response was confirmed by real-time PCR analysis of increased interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis factor alpha ($TNF-{\alpha}$) expression levels. In TLR-4-activated chondrocytes, proteomic changes were determined by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectroscopy analysis, and genomic changes were determined by microarray and gene ontology analyses. Proteomics analysis identified 26 proteins with significantly altered expression levels; these proteins were related to the cytoskeleton and oxidative stress responses. Gene ontology analysis indicated that LPS treatment altered specific functional pathways including 'chemotaxis', 'hematopoietic organ development', 'positive regulation of cell proliferation', and 'regulation of cytokine biosynthetic process'. Nine of the 26 identified proteins displayed the same increased expression patterns in both proteomics and genomics analyses. Western blot analysis confirmed the LPS-induced increases in expression levels of lamin A/C and annexins 4/5/6. In conclusion, this study identified the time-dependent genomic, proteomic, and functional pathway alterations that occur in chondrocytes during LPS-induced TLR-4 activation. These results provide valuable new insights into the underlying mechanisms that control the development and progression of osteoarthritis.

• Nutrition Research and Practice
• /
• v.6 no.2
• /
• pp.97-105
• /
• 2012

$Schizandra$ $chinensis$ Baillon is a traditional folk medicine plant that is used to treat and prevent several inflammatory diseases and cancer in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. This study was designed to investigate mechanisms of anti-allergic activity of a $Schizandra$ $chinensis$ Baillon water extract (SCWE) in immunoglobulin E (IgE)-antigen complex-stimulated RBL2H3 cells and to assess whether gastric and intestinal digestion affects the anti-allergic properties of SCWE. Oxidative stress is an important consequence of the allergic inflammatory response. The antioxidant activities of SCWE increased in a concentration-dependent manner. RBL-2H3 cells were sensitized with monoclonal anti-dinitrophenol (DNP) specific IgE, treated with SCWE, and challenged with the antigen DNP-human serum albumin. SCWE inhibited ${\beta}$-hexosaminidase release and expression of interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-${\alpha}$) mRNA and protein in IgE-antigen complex-stimulated RBL2H3 cells. We found that digested SCWE fully maintained its antioxidant activity and anti-allergic activity against the IgE-antigen complex-induced activation of RBL-2H3 cells. SCWE may be useful for preventing allergic diseases, such as asthma. Thus, SCWE could be used as a natural functional ingredient for allergic diseases in the food and/or pharmaceutical industries.

• Environmental Mutagens and Carcinogens
• /
• v.22 no.2
• /
• pp.112-124
• /
• 2002

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to exert detrimental toxicities on various organ systems including reproductive, cardiovascular, nervous, or dermal system. Immunomodulatory effects of TCDD is thymic atrophy, downregulation of cytotoxic T or B lymphocyte differentiation and activation, which were demonstrated using experimental animals, whereas immunotoxicity in human has not been investigated well. This study was proceeded to evaluate general immunologic spectrum of the Korean Vietnam War veterans exposed to TCDD during their operation, and compare with that of the non-exposed control subjects with similar age. Regarding composition and quantity, immune cells in peripheral blood collected from the TCDD-exposed was not much different from those of the control except decreased red blood cell, hemoglobin and hematocrit level. Furthermore, plasma IgG2, G3, and G4 isotype distribution was similar between two groups, but IgG1 level was significantly lowered in the TCDD-exposed, indicating a TCDD-mediated functional alteration of B cells. Significantly enhanced level of IgE in plasma, a hallmark of dermal or respiratory allergic response, was also observed in the TCDD-exposed compared with that of the control. Elevated generation of IL-4 and IL-10 was resulted from in vitro stimulation of T cells with PMA plus ionomycin or PHA, respectively, from the TCDD-exposed in comparison to those of the control, suggesting a skewed type-2 response. In addition, the level of IFN${\gamma}$, a multifunctional cytokine for T cell-mediated immunity, was lowered in the TCDD-exposed with upregulation of tumor necrosis factor $\alpha$. The present study suggests that TCDD exposure disturbs immunohomeostasis in humans observed as an aberrant plasma IgE and IgG1 levels and dysregulation of T cell activities.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.42 no.10
• /
• pp.1576-1584
• /
• 2013

This study is carried out to assess the relative effects of different doses of dietary glucose or fructose on non-alcoholic fatty liver disease (NAFLD) and hepatic metaflammation in a rodent model of type 2 diabetes. KK/HlJ male mice were fed experimental diets as follows: 1) control (CON), 2) moderate glucose (MG, 30% of total calories as glucose), 3) high glucose (HG, 60% of total calories as glucose), 4) moderate fructose (MF, 30% of total calories as fructose), and 5) high fructose (HF, 60% of total calories as fructose) for three weeks. Food intake was not affected by treatments. Compared with HF, HG not only increased serum fasting glucose and area under the curve during oral glucose tolerance test, but also decreased the levels of serum insulin and adiponectin. It indicated that glucose control was complicated via high glucose intake. High fructose treatment led to increased triglyceride in the serum and liver. In comparison to HG, high fructose diet activated NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome consisting of apoptosis-associated speck-like protein containing a CARD (ASC), NLRP3 and caspase 1, which increases interleukin (IL)-$1{\beta}$ maturation and secretion. The activation of NLRP3 inflammasome was accompanied by increased levels of tumor necrosis factor alpha (TNF-${\alpha}$) and IL-6. However, the expression of NLRP3 inflammasome components and pro-inflammatory cytokines did not differ between CON and HG. These data suggested that dietary fructose triggers hepatic metaflammation accompanied by NLRP3 inflammasome activation and has deleterious effects on NAFLD.

• Toxicological Research
• /
• v.28 no.1
• /
• pp.5-9
• /
• 2012

It has been shown that the accumulation of prion in the cytoplasm can result in neurodegenerative disorders. Synthetic prion peptide 106-126 (PrP) is a glycoprotein that is expressed predominantly by neurons and other cells, including glial cells. Prion-induced chronic neurodegeneration has a substantial inflammatory component, and an increase in the levels of matrix metalloproteinases (MMPs) may play an important role in neurodegenerative development and progression. However, the expression of MMPs in PrP induced rat astrocytes and microglia has not yet been compared. Thus, in this study, we examined the fluorescence intensity of CD11b positive microglia and Glial Fibrillary Acidic Protein (GFAP) positive astrocytes and found that the fluorescent intensity was increased following incubation with PrP at 24 hours in a dose-dependent manner. We also observed an increase in interleukin-1 beta (IL-$1{\beta}$) and tumor necrosis factor alpha (TNF-${\alpha}$) protein expression, which are initial inflammatory cytokines, in both PrP induced astrocytes and microglia. Furthermore, an increase MMP-1, 3 and 11 expressions in PrP induced astrocytes and microglia was observed by real time PCR. Our results demonstrated PrP induced activation of astrocytes and microglia respectively, which resulted in an increase in inflammatory cytokines and MMPs expression. These results provide the insight into the different sensitivities of glial cells to PrP.

• Biomolecules & Therapeutics
• /
• v.24 no.6
• /
• pp.595-603
• /
• 2016

(E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to ${\beta}$-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-${\kappa}B$ activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-${\kappa}B$-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-${\kappa}B$ and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

• Food Science of Animal Resources
• /
• v.31 no.5
• /
• pp.701-709
• /
• 2011

This study was performed to establish an effective extraction method of pig placenta extract that could be used for a putative functional food supplement with immunomodulatory effects. In the present study, we used different temperatures (4, 37, 60, 80, and $100^{\circ}C$) and different solvents (chloroform, NaOH, and phosphate buffered saline [PBS]) to extract the pig placenta. Among the different placenta extracts yielded by the different extraction methods, placenta extract (PE) in PBS at $80^{\circ}C$ for 30 min (referred to as PE-PBS80) showed a significant increase of nitric oxide production of up to 22.97 ${\mu}M/10^5$ cells at a 1 mg/mL dose (p<0.05 ) in J774A.1 cells than other extracts and control tested. Using PE-PBS80, further animal challenges were performed to identify the immune-enhanced effects. As a result, orally administered PE-PBS80 showed a significant increase in blood T and B cell activities and immunoglobulin (IgG and IgM) production. IgG and IgM levels increased to 41.53 mg/mL at a 20 mg dose on day 7 and to 27.38 mg/mL at a 10 mg dose on day 14, respectively (p<0.05). Furthermore, PE-PBS80 was also able to significantly enhance the immune modulator cytokine levels (p<0.05) compared to the control and vehicle treatments. Among the evaluated cytokines, the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level increased to 28.89 pg/mL at extract doses of 20 and 50 mg, the interleukin-$1{\beta}$ (IL-$1{\beta}$) level increased to 21.52 pg/mL at extract doses of 10, 20, 50 and 75 mg and the interferon (IFN)-${\gamma}$ level increased to 18.24 pg/mL at extract doses of 10, 20, and 50 mg. Therefore, this study presents an effective method for extracting pig placenta extracts and also demonstrates that pig placenta extracts had significant immunomodulatory effects not only at the cellular level but also in a mouse model, suggesting that this material could be used as an excellent candidate functional food supplement.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.39 no.8
• /
• pp.1213-1219
• /
• 2010

We evaluated the anti-aging potential and safety of black garlic extract for cosmeceutical ingredient. Black garlic was made by spontaneous fermentation for 40 days at $60{\sim}70^{\circ}C$, 85~95% RH without any additives. The 10% black garlic extract had sweet odor, antioxidant activities and inhibitory activities of skin againg enzymes such as tyrosinase and elastase. The skin safety was performed to evaluate of potential toxicity using the primary irritation test and skin sensitization test. The black garlic extract did not show any adverse reactions such as erythema and edema on intact skin sites at primary irritation test, but on abraded sites, some experimental animals showed very slight erythema. So, the black garlic extract was classified as a practically non-irritating material based on the score 0.23 of primary irritation index. The skin sensitization study was tested by the guinea pig maximization test (GPMT) and Freund's complete adjuvant (FCA) with intradermal injection of 10% black garlic extract. The skin sensitization test showed no skin sensitization. The allergic sensitization depends on tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6). The concentration of IL-6 on challenged tissue of treated with black garlic extract was not significantly different with negative control group (saline treated group). Based on this study, the potential for black garlic as a cosmeceutical ingredient was proven.