• Journal of Ginseng Research
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• v.31 no.4
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• pp.181-190
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• 2007

Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-${\kappa}B$, and expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-${\kappa}B$ activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.10
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• pp.1371-1377
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• 2012

Biological activities of Korean Panax ginseng 55% ethanol extract (KPGE) were investigated. The measured total polyphenol content of KPGE was 357.45 mg/100 g. KPGE showed the highest ${\alpha},{\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) radical scavenging activities of 80% and 86% at 1,000 ${\mu}g/mL$, respectively. DPPH and ABTS radical scavenging activities significantly increased in a KPGE concentration-dependent manner. SOD-like activity of KPGE (1, 10, and 100 ${\mu}g/mL$) increased from 22% up to 33% at KPGE concentrations of 500 and 1,000 ${\mu}g/mL$. KPGE treatment significantly suppressed the generation of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and cytokines (tumor necrosis factor-alpha: TNF-${\alpha}$, interleukin-6: IL-6, interleukin-$1{\beta}$: IL-$1{\beta}$), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. KPGE demonstrated strong anti-inflammatory activity that reduced NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells. Even low concentrations of KPGE (1 and 10 ${\mu}g/mL$) reduced $PGE_2$ and NO production in RAW 264.7 macrophages without LPS-stimulation, respectively. At concentrations of 100, 500, and 1,000 ${\mu}g/mL$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 production were significantly suppressed. The results of our study suggest the potential of Korean Panax ginseng as an excellent antioxidant substance for inhibiting inflammatory mediators. Therefore, Korean Panax ginseng (KPGE) may be used as a therapeutic approach to various inflammatory diseases.

• Journal of the Korean Applied Science and Technology
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• v.41 no.3
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• pp.745-755
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• 2024

Calystegia pubescens Lindl. (C. pubesens) is a native Korean herb that has been traditionally used for its diuretic, fatigue, and blood sugar-lowering effects. In previous studies, C. pubesens has shown antioxidant and whitening effects, but research on its antibacterial and anti-inflammatory properties is limited, and its potential as functional materials is lacking. In this study, we investigated the antibacterial, antioxidant, and anti-inflammatory effects of leaf (CPL) and stem (CPS) extracts of C. pubesens extracted with 70% ethanol. When the anti-bacterial effect was confirmed, CPL showed superior anti-bacterial effect than CPS for C. acne, S. aureus, E. coli and P. aeruginosa. Additionally, CPL exhibited significantly higher antioxidant activity compared to CPS, as demonstrated by DPPH and ABTS⁺ radical scavenging assays. Therefore, CPL showed superior anti-bacterial and antioxidant effects compared to CPS. Based on these results, further investigation was conducted to confirm the anti-inflammatory effect of CPL using RAW264.7 macrophages. Nitric oxide (NO) produced by lipopolysaccharide (LPS) stimulation was significantly reduced by CPL treatment in a dose-dependent manner. Additionally, the protein and mRNA expression of iNOS was reduced by CPL in LPS-indueced RAW264.7 cells, which was consistent with NO production. In conclusion, this study confirmed that CPL has superior anti-bacterial and antioxidant effects compared to CPS, and demonstrated anti-inflammatory effect of CPL via inhibiting iNOS expression and NO production induced by LPS. Based on the result, we suggest the potential of CPL as a valuable functional materials.

• Journal of Nutrition and Health
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• v.42 no.3
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• pp.207-212
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• 2009

Codonopsis lanceolatae has been used as one of the traditional remedies as well as food source. However, few studies on their immunomodulating effects have been reported. We previously reported that ex vivo supplementation of Codonopsis lanceolatae water extracts enhanced splenocyte proliferation compared to the control group. In order to elucidate its ex vivo effect, six to seven week old balb/c mice were fed ad libitum on a chow diet and water extracts of Codonopsis lanceolatae were orally administrated every other day for four weeks at two different concentrations (50 and 500 mg/kg B.W). After preparing the single cell suspension, the proliferation of splenocytes was determined by MTT (3- [4,5-dimethylthiazol-2-y] -2,5-diphenyl terazolium bromide) assay. The production of cytokine (IL-1${\beta}$, IL-6, TNF-${\alpha}$), secreted by macrophages stimulated with LPS or not, was detected by ELISA assay using a cytokine kit. After 48 hrs of incubation with the mitogen (ConA or LPS) stimulation, the mice splenocyte proliferation in experimental group was statistically increased at two different concentrations than that in control group. The cytokines production was more significantly enhanced at the lower supplementation (500 mg/kg B.W.) group rather than higher concentration (500 mg/kg B.W.) compared to the control group. The results of this study may suggest that the supplementation of water extract of plant mixture could regulate the immune function by increasing the splenocyte proliferation and enhance the immune function through regulating cytokine production capacity by activated macrophages in mice.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.221-231
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• 2005

Background: Immune regulatory dendritic cells (DCs) play an important role in maintaining self-tolerance. Recent evidences demonstrate that DCs expressing indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan catabolism, play an important role in immunoregulation and tolerance and induce T cell apoptosis. This study was devised to examine the role of IDO in the oral tolerance induction in collagen-induced arthritis (CIA) mouse model. Methods: Beginning 2 weeks before immunization, CII was fed six times to DBA/1 mice and the effect on arthritis was assessed. In tolerized mice, $CD11c^+$ DCs were isolated and stimulated with CII, IFN-${\gamma}$, and LPS with or without IDO inhibitor, 1-methyl-DL-tryptophan (1-MT) and IDO expression by $CD11c^+$ DCs was analyzed using FACS and RT-PCR. The expression of IDO, MHC II, CD80, and CD86 by $CD11c^+$ DCs were examined using confocal microscopy. Regulatory effect of $CD11c^+$ DCs on Ag-specific T cell proliferative response to CII was examined by mixed lymphocyte reaction (MLR) with or without 1-MT. Results: The proportion of IDO-expressing $CD11c^+$ DCs was slightly higher in tolerized mice than in CIA mice and significantly increased after stimulation with CII, IFN-${\gamma}$, and LPS in an IDO-dependent manner. On confocal microscopic examination, the expression of IDO was higher and those of MHC II and CD86 were lower in CD11c + DCs from tolerized mice compared to those from CIA mice. On MLR, $CD11c^+$ DCs from tolerized mice inhibited T cell proliferative response to CII in an IDO-dependent manner. Conclusion: Enhanced IDO expression by $CD11c^+$ DCs from tolerized mice may contribute to the regulation of proliferative response of CII-reactive T cells and could be involved in the induction of oral tolerance to CII.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.1
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• pp.1-9
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• 2017

Acer tegmentosum Maxim (ATM) is known as traditional medicine for treatment of hepatic disorders such as hepatitis, related-inflammatory disease, and hepatic cancer. In this study, we evaluated the antioxidant and anti-inflammatory effects of ATM extracted with $80^{\circ}C$ water or 95% ethanol. Antioxidant activities of ATM extracts were measured based on DPPH and ABTS radical scavenging activities, total polyphenolic compound contents, and ferric reducing antioxidant power. The anti-inflammatory effects of ATM extract were assayed on release of nitric oxide, tumor necrosis factor $(TNF)-{\alpha}$, and interferon $(IFN)-{\gamma}$ from lipopolysaccharide (LPS)-induced macrophages. In these experiments, 95% ethanol extract of ATM showed stronger antioxidant and anti-inflammatory effects than water extract. Therefore, we determined the effects of ATM ethanol extract on an animal model of sepsis. Seven days oral gavage of ATM ethanol extract followed by LPS stimulation reduced the protein levels of $TNF-{\alpha}$ and $IFN-{\gamma}$ in serum as well as mRNA levels of $TNF-{\alpha}$ and interleukin-6 in intestinal epithelial cells. In addition, ATM ethanol extract reduced DNA damage in mouse lymphocytes. These results indicate that ATM extract has strong antioxidant and anti-inflammatory in vitro and in vivo effects and may be developed as a potential food material for prevention of inflammatory diseases.

• Biomedical Science Letters
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• v.5 no.1
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• pp.85-93
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• 1999

Nitric oxide (NO) plays an important role in immunologic defense, and influences upon the functioning of secretory tissues and cells. It also exhibits cytotoxic/cytostatic activity as one of major operating effectors of the cellular immunity system. We investigated the effects of serum on the cell damages and NO production in the mouse liver cell line BNL CL.2 to establish the role of NO. We observed that, when BNL CL.2 cells were cultured in serum-free medium, they were induced to cell damage by the stimulation of IFN-$\gamma$ alone or IFN-$\gamma$ plus LPS. Serum-starved cells showed large amount of nitrite accumulation and NO synthase (NOS) expression in response to IFN-$\gamma$ alone in dose- and time- dependent manners, but serum-supplied cells did not The production of NO was blocked by protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin. These results suggest that the deprivation of serum in the BNL CL.2 cell culture medium might primed with the cells to produce NO when the cells are triggered by IFN-$\gamma$ and the involvement of PTK signal transduction pathway in the expression of NOS gene in murine hepatocytes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.616-623
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• 2010

Three herbal formulas (Bangpungtongsung-san, Ohyaksungi-san, and Ojeok-san) for wind-cold and heat pain symptom were applied to investigate the immunological activities on antigen (Ag)-specific or Ag-non-specific immune responses in murine macrophage cell line (RAW 264.7) and ovalbumin (OVA)-immunized mice. This study was carried out in nitric oxide (NO) synthesis in RAW 264.7 cells and cellular proliferation in mouse splenocytes according to three herbal formulas. C57BL/6 mice were immunized intraperitonially with OVA/aluminium ($100\;{\mu}g/200\;{\mu}g$/mouse) on day 1, 8, and 15. Three herbal formulas were administrated to mice orally for 3 weeks from day 1. On day 22, OVA-, lipopolysaccharide (LPS)-, and concanavalin A (Con A)-stimulated splenocyte proliferation and antibodies (OVA-specific antibodies of the IgG, lgG1, and total IgM classes) in plasma were measured. Ohyaksungi-san increased NO synthesis in RAW 264.7 cells. Ojeok-san and Ohyaksungi-san significantly enhanced cellular proliferation by LPS and Con A in splenocytes from OVA-immunized mice (p<0.001). Three herbal formulas for wind-cold and heat pain symptom also significantly enhanced plasma OVA-specific IgG, IgG1, and total IgM levels compared with the OVA/Alum group. These results suggested that three herbal formulas for wind-cold and heat pain symptom could be used as stimulator of immune response.

• Journal of Applied Biological Chemistry
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• v.55 no.1
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• pp.41-46
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• 2012

Arabinoxylan (Ara) rice bran has been shown to be a potent biological response modifier as manifested by stimulation of different arms of the immune system. We examined the effects of Ara rice bran and exercise on the immune function and cytokines in lipopolysaccharide (LPS)-stimulated rats. As the results, tumor necrosis factor-${\alpha}$ as representative inflammatory cytokines showed a significantly lower in Ara supplement group, thus the Ara rice bran had a higher inhibitory activity than the both exercise and control group. However, 4 weeks of exercise training significantly increased inflammatory reactions rather than treatment with Ara in LPS-treated rats. The Ara rice bran acted to decrease the inflammatory reaction. These results suggest that the supplement of Ara rice bran is likely contribute to inflammation response and the Ara rice bran can be used as a possible safe alternative to the immunotherapeutic modalities.

• The Korean Journal of Food And Nutrition
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• v.20 no.1
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• pp.74-78
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• 2007

Ixeris sonchifolia Hance(Godulbaegi), Oenanthe javanica(Dolminari), Fagopyrum esculentum Moench(Buckwheat), Hizikia fusiforme(Seaweed Fusiforme) and Zingiber officinale Roscoe(Ginger) have all been used as one of the traditional remedies as well as food source. There are few studies However, on their immunomodulating effects have been reported. We previously reported that ex vivo supplementation of each of the Ish, Oj, Fem, Hf and Zor water extracts enhanced the splenocytes proliferation compared to the control group. In this study, the combined immunomodulative effects of a plant water extract mixture containing these five food sources(Ish+Oj+Fem+Hf+Zor) was compared to the individual effect of each. The production of cytokine(IL-1${\beta}$, IL-6, and TNF-${\alpha}$), secreted by macrophages stimulated with LPS or without, were detected via ELISA assay using a cytokine kit. After 48hrs of incubation with mitogen(ConA or LPS) stimulation, the mouse splenocyte proliferation in the experimental group had significantly increased at two different concentrations compared to the control group. The results of this study may suggest that the supplementing with a plant water extract mixture could regulate immune function by increasing splenocyte proliferation as well as enhance immune function by regulating the cytokine production capacity activated macrophages in mice.