• Title/Summary/Keyword: cytokines production

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Structural characteristics of a red ginseng acidic polysaccharide rhamnogalacturonan I with immunostimulating activity from red ginseng

  • Lee, Sue Jung;In, Gyo;Han, Sung-Tai;Lee, Mi-Hyang;Lee, Jong-Won;Shin, Kwang-Soon
    • Journal of Ginseng Research
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    • v.44 no.4
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    • pp.570-579
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    • 2020
  • Background: Many researchers reported that the various immune activities of red ginseng are due to acid polysaccharides. But, the exact structural characteristics of the acidic polysaccharide in red ginseng have not been fully elucidated. Therefore, we isolated the acidic polysaccharide from red ginseng and characterized the structural property of the active moiety of this polysaccharide, which contributes to the immunostimulatory activity of red ginseng. Methods: A polysaccharide (RGP-AP-I) was purified from red ginseng via size-exclusion chromatography using Sephadex G-100. Immunostimulatary activity of RGP-AP-I was investigated via anti-complementory and macrophage stimulatory activity. The structure of RGP-AP-I was characterized by HPLC, sugar composition, β-glucosyl Yariv reagent and methylation analysis. Results: Peritoneal macrophages stimulated using RGP-AP-I significantly augmented the production of various cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-α. The primary structure of RGP-AP-I was elucidated by assessing its sugar composition and methylation analysis. RGP-AP-I is a 96 kDa acidic polysaccharide, and comprises nine different monosaccharides, which mainly include sugars such as rhamnose (Rha, 9.5%), galacturonic acid (GalA, 18.4%), galactose (Gal, 30.4%), and arabinose (Ara, 35.0%). RGP-AP-I exhibited an considerable reaction with the β-glucosyl Yariv reagent, revealing the presence of arabino-β-3,6-galactan. Methylation analysis indicated that RGP-AP-I comprises 21 different glycosyl linkages, such as 3-, 4-, 6- and 3,6-linked Galp; 5-linked Araf; 2,4-linked Rhap; and 4-linked GalAp, which are characteristics of rhamnogalacturonan I (RG-I). Conclusion: we assumed that the immunostimulatory activity of RGP-AP-I may be due to the RG-I structure, which comprises a main chain with a repeating linkage unit, [→2)-Rhap-(1→4)-GalAp-(1→] and three groups of side chains such as (1→5)-linked arabinan, (1→4)-linked galactan, and arabino-β-3,6-galactan, which branch at the C(O)4 positions of Rha residues in the main chain of RGP-AP-I.

Effects of Gamigwichulpajing-Tang on the Development of Experimentally-induced Endometriosis in Rats (가미귀출파징탕(加味歸朮破?湯)이 실험적으로 유발된 흰쥐의 자궁내막증에 미치는 영향)

  • Kim, Yeo-Yae;Lee, Dong-Nyung;Seo, Il-Bock;Kim, Hyung-Jun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.19 no.2
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    • pp.162-185
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    • 2006
  • Purpose : This study was carried out to investigate the effects of Gamigwichulpajing-Tang(GGT) on the development of experimentally-induced endometriosis in rats. Materials and Methods : Endometriosis was induced in rats by auotransplanting uterine tissue to the peritoneum and devided them into three groups: (1) sham-operated group(n=8), (2) surgically induced endometriosis and untreated control group(n=8), (3)surgically induced endometriosis and GGT treated group. GGT(700mg/head) was orally administrated for 15days after operation. Then we measured the body weight, the volumes of endometriotic implants, the weight of uterus and ovary, and investigated the content of cytokines(MCP-1, $TNF-{\alpha}$, $IL-l{\beta}$) in serum and ascites. Histopathology, immunohistochemistry for COX-2, and histochemistry for mast cell in transplanted uterine tissue were performed. Results :- The $volume(mm^3)$ of endometriotic implants in GGT-treated group$(53.50\;{\pm}18.63)$ was significantly decreased(p<<0.01) compared with control group$(404.50{\pm}317.68)$. - The content(pg/ml) of MCP-1 in ascites in GGT-treated group$(4265{\pm}108)$ was significantly decreased(p<<0.001) compared with control group$(8632{\pm}1245)$. - The content(pg/ml) of $TNF-{\alpha}$ in serum in GGT-treated group$(64.5{\pm}21.6)$ was significantly decreased(p<<0.05) compared with control group$(147.1{\pm}78.2)$. - The content(pg/ml)- of $TNF-{\alpha}$ in ascites in GGT-treated group$(738.3{\pm}502.4)$ was significantly decreased(p<<0.05) compared with control group$(1245.2{\pm}362.2)$. - The percentage(%) of positive epithelial layers for COX-2 in GGT-treated group$(22.9{\pm}9.3)$ was significantly decreased(p<<0.001) compared with control group$(50.2{\pm}8.2)$. - The number of mast cells in adjacent tissue of transplanted uterine tissue in GGT-treated group$(61.4{\pm}13.9)$ was significantly decreased(p<<0.001) compared with control group$(109.3{\pm}30.2)$. - The number of mast cells in stroma of transplanted uterine tissue in GGT-treated group$(9.4{\pm}2.7)$ was significantly decreased(p<<0.001) compared with control group$(26.0{\pm}7.7)$. - Histopathologically, proliferation of endomeuiotic epithelia and stroma, and infiltration of inflammatory cells in transplanted uterine tissue of GGT-treated group were weakly observed than those of control group. Conclusion :On the basis of these results, we concluded that Gamigwichulpajing-Tang have inhibiting effects on the development of transplanted uterine tissue. And these effects may be related with decreased Production of MCP-1 and $TNF-{\alpha}$, decreased expression of COX-2, and decreased infiltration of mast cells by administration of Gamigwichulpajing-Tang.

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A Screen for Dual-protection Molecules from a Natural Product Library against Neuronal Cell Death and Microglial Cell Activation (신경세포 사멸과 미세아교세포활성화 억제 동시 가능 천연물질 탐색 연구)

  • Min, Ju-Sik;Lee, Dong-Seok
    • Journal of Life Science
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    • v.25 no.6
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    • pp.656-662
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    • 2015
  • Natural products and natural product structures play a general and highly significant role in drug discovery and development process because it has various merits and potentials for new drug source that have extensive clinical experience, development time contraction, excellent stability and safety. In several neurological disorders, neuronal death and excessive activation of microglia (neuro-inflammation) are observed. A number of drug discovery-related neuronal cell death and neuro-inflammation was studied from natural products, respectively. However, until now, it has not been possible to study dual-protection molecules recorded in the Natural Product library. In the present study, using the natural product-derived library of the Institute for Korea Traditional Medical Industry, we investigated dual-protective molecules against glutamate (a classical excitatory neurotransmitter)-induced oxidative stress mediated neuronal cell death and LPS-induced excessive activated microglial cells (immune cells of the brain). Chrysophanol, extracted from Rheum palmatum, had dual-protective effects against both glutamate-induced neuronal cell death and LPS-induced NO production, triggering proinflammatory cytokines and microglia activation and resulting in neuroinflammation. Flow-cytometry analysis revealed that chrysophanol had a scavenger effect, scavenging glutamate- and LPS-induced reactive oxygen species (ROS) produced by neuronal and microglial cells, respectively. Based on the present study, chrysophanol may have an important protective role against neuronal cell death and neuroinflammation in the brain. The results may be helpful for studying drug development candidates for treating central nervous system disorders.

Inhibition of Interleukin-1α-induced Intestinal Epithelial Tight Junction Permeability by Curcumin Treatment in Caco-2 Cells in Caco-2 Cells (Caco-2 세포에서 커큐민 처리에 의한 IL-1α로 유도된 소장 상피세포의 tight junction 투과성 저해)

  • Kim, Choon Young
    • Journal of Life Science
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    • v.26 no.9
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    • pp.1082-1087
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    • 2016
  • The intestinal tight junction (TJ) plays an important role as a paracellular barrier. Impaired TJ permeability and enhanced proinflammatory cytokine production are crucial pathophysiological mechanisms in inflammatory bowel diseases (IBDs). Although proinflammatory cytokines, tumor necrosis factor-alpha and interluekin-1 beta, which are markedly increased in IBD patients, have been reported to increase intestinal TJ permeability, the role of interleukin-1 alpha (IL-1α) in the TJ has not been studied. Phytochemicals could prevent proinflammatory cytokine-caused TJ alteration. Curcumin (CCM), a biologically active component of turmeric, has a strong anti-inflammatory activity. The purpose of this study was to elucidate the effect of IL-1α on intestinal epithelial TJ permeability and the role of CCM in IL-1α′s action on TJ in an in vitro intestinal epithelial system, Caco-2 monolayers. The TJ integrity of Caco-2 monolayers was estimated by measuring the flux of FITC-labeled dextran and transepithelial electrical resistance (TEER). Apical IL-1α (100 ng/ml) treatment elevated TJ permeability and suppressed TEER of Caco-2 monolayers. Pretreatment with CCM (20 μM) for 30 min significantly inhibited IL-1α-induced TJ alterations, such as increased TJ permeability and decreased in TEER values. These results demonstrated that IL-1α-induced increases in Caco-2 TJ permeability and CCM blocked the action of IL-1α in the TJ.

Antioxidant, Antimicrobial and Anti-inflammatory Activities of Essential Oil from Erigeron annuus L. Flower (개망초꽃 에센셜 오일의 항산화, 항균 및 항염 활성)

  • Yi, Mi-Ran;Jeon, Ah-Lim;Kang, Chang-Hee;Bu, Hee-Jung
    • Journal of the Korean Applied Science and Technology
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    • v.33 no.4
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    • pp.717-725
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    • 2016
  • This study was designed to examine the in vitro antioxidant, antimicrobial and anti-inflammation effects of essential oils of Erigeron annuus L. Flower. Erigeron annuus L. essential oils were obtained by solvent extraction. Antioxidative ability was evaluated by bioassays using ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid diammonium salt) radical scavenging effect and 2, 2-diphenyl-1-1-picrydrazyl (DPPH) free radical scavenging activity. Erigeron annuus L. essential oil exhibited free radical scavenging activity on ABTS and DPPH 98.6%, 48.3% respectively, at a concentration of $500{\mu}g/ml$. Antimicrobial activity of essential oils of Erigeron annuus L. were tested against Staphylococcus aureus (S. aureus), Propionibacterium acnes (P. acne) and Escherichia coli (E. coli) by paper disc method, MIC and MBC. Erigeron annuus L. essential oil showed excellent antibacterial activities against S. aureus with MIC and MBC values of 0.31 mg/mL. The clear zone, indicating antimicrobial activity against P. acnes, was 14 mm, MIC and MBC values 0.31 mg/mL, 0.63 mg/mL, respectively. For the anti-inflammatory activity in RAW 264.7 cell, the Erigeron annuus L. essential oils inhibited not only NO production but also the expression of pro-inflammatory cytokines such as, TNF-${\alpha}$, IL-6 in a dose-dependent manner. These results suggested that Erigeron annuus L. essential oils has considerable potential as a cosmetic ingredient with antioxidative, antimicrobial and anti-inflammation effects.

Biological Activities of Yellow Garlic Extract (황마늘 추출물의 생리활성)

  • Kang, Jae Ran;Hwang, Cho Rong;Sim, Hye Jin;Kang, Min Jung;Kang, Sang Tae;Shin, Jung Hye
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.7
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    • pp.983-992
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    • 2015
  • This study investigated the quality characteristics and biological activities, such as antioxidant, whitening, anti-diabetes, and anti-inflammatory activities, of yellow garlic, by simplify processing time and manufacturing process compared with black garlic. Extracts were prepared various ratios of water and ethanol solvent [water : ethanol (v/v)=100:0, 70:30, 50:50, 30:70, 0:100] from yellow garlic. Alliin content of yellow garlic showed no difference compared with fresh garlic, whereas S-allyl cysteine content of yellow garlic was higher than that of fresh garlic. Alliin content of yellow garlic extracts increased in an ethanol concentration-dependent manner. Total phenol and flavonoid contents were highest in 100% ethanol extract. DPPH and ABTS radical scavenging abilities did not show significant differences among 0~70% ethanol extracts, whereas 100% ethanol extract showed the highest contents of 93.45% and 91.46%, respectively. Tyrosinase and ${\alpha}$-glucosidase inhibitory activities were also highest in 100% ethanol extract, but did not show significant differences among the extract solvents. Water and ethanol extracts from yellow garlic showed anti-inflammatory effects by modulating production of NO and cytokines at a concentration of $100{\mu}g/mL$. We suggest that yellow garlic has antioxidant, whitening, anti-diabetes, and anti-inflammatory activities and can be used as a functional material similar to black garlic.

Mechanism underlying NO-induced apoptosis in human gingival fibroblasts

  • Hwang, In-Nam;Jeong, Yeon-Jin;Jung, Ji-Yeon;Lee, Jin-Ha;Kim, Kang-Moon;Kim, Won-Jae
    • International Journal of Oral Biology
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    • v.34 no.1
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    • pp.7-14
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    • 2009
  • Nitric oxide (NO) acts as an intracellular messenger at the physiological level but can be cytotoxic at high concentrations. The cells within periodontal tissues, such as gingival and periodontal fibroblasts, contain nitric oxide syntheses and produce high concentrations of NO when exposed to bacterial lipopolysaccharides and cytokines. However, the cellular mechanisms underlying NO-induced cytotoxicity in periodontal tissues are unclear at present. In our current study, we examined the NO-induced cytotoxic mechanisms in human gingival fibroblasts (HGF). Cell viability and the levels of reactive oxygen species (ROS) were determined using a MTT assay and a fluorescent spectrometer, respectively. The morphological changes in the cells were examined by Diff-Quick staining. Expression of the Bcl-2 family and Fas was determined by RT-PCR or western blotting. The activity of caspase-3, -8 and -9 was assessed using a spectrophotometer. Sodium nitroprusside (SNP), a NO donor, decreased the cell viability of the HGF cells in a dose- and time-dependent manner. SNP enhanced the production of ROS, which was ameliorated by NAC, a free radical scavenger. ODQ, a soluble guanylate cyclase inhibitor, did not block the SNP-induced decrease in cell viability. SNP also caused apoptotic morphological changes, including cell shrinkage, chromatin condensation, and DNA fragmentation. The expression of Bax, a member of the proapoptotic Bcl-2 family, was upregulated in the SNP-treated HGF cells, whereas the expression of Bcl-2, a member of the anti-apoptotic Bcl-2 family, was downregulated. SNP augmented the release of cytochrome c from the mitochondria into the cytosol and enhanced the activity of caspase-8, -9, and -3. SNP also upregulated Fas, a component of the death receptor assembly. These results suggest that NO induces apoptosis in human gingival fibroblast via ROS and the Bcl-2 family through both mitochondrial- and death receptor-mediated pathways. Our data also indicate that the cyclic GMP pathway is not involved in NO-induced apoptosis.

Comparison of Anti-Inflammatory Activity of Spirulina maxima Extract by Ultrasonication and Water Extraction Process (Spirulina maxima의 초음파 및 열수 추출 공정에 따른 항염증 효과 비교 탐색)

  • Sin, Jae Bin;Choi, Woon Yong;Kang, Do Hyung;Lee, Hyeon Yong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.12
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    • pp.1852-1857
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    • 2014
  • The aim of this study was to compare the anti-inflammatory activities of Spirulina maxima treated with ultrasonication and water extraction process. S. maxima extracted via ultrasonication showed low cytotoxicity (16.90%) in a normal human cell line, CCD-986sk. Especially, S. maxima ultrasonication extract showed the highest DPPH radical scavenging activities (46.82%) compared to water extract (31.30%) at $100^{\circ}C$. In addition, ultrasonication extract showed a high amount of flavonoids (21.60 mg/g) and total phenols ($8.36{\mu}g/mL$). Nitric oxide production by 1.0 mg/mL of S. maxima ultrasonication extract strongly inhibited ($1.3770{\mu}M$), whereas water extract showed lower inhibition ($1.5784{\mu}M$). TNF-${\alpha}$ and IL-6 cytokines were effectively inhibited by 1.0 mg/mL of S. maxima ultrasonication extract, which shows strong antioxidant activities. Based on these results, it can be concluded that the ultrasonication process increase anti-inflammatory activity of S. maxima extract.

Anti-inflammatory Effect of Onion (Allium cepa) Peel Hot Water Extract in vitro and in vivo (양파껍질 열수추출물의 in vitro 및 in vivo 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Ahn, Na-Kyung;Choi, Yeon-Uk;Kim, Min-ji;Bark, Si-Woo;Pak, Won-Min;Kim, Bo-Ram;Park, Ji-Hye;Bae, Nan-Young;Ahn, Dong-Hyun
    • KSBB Journal
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    • v.30 no.4
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    • pp.148-154
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    • 2015
  • Onion (Allium cepa) is one of the flavonoids-rich materials in human diet and onion peel, which is the onion by-products, contains over 20 times more quercetin than the flesh. In this study, to examine the anti-inflammatory effects of onion peel hot water extract (OPHWE), the cell viability, nitric oxide (NO), pro-inflammatory cytokines, such as interluekin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and IL-$1{\beta}$, were measured using the murine macrophage cell line RAW 264.7 cells. The Balb/c mice were used for an in vivo acute toxicity test and ICR mice were used for measurement of inhibition effects of croton oil-induced mouse ear edema. As a result, NO levels decreased in a dose-dependent manner. The production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed by 38%, 41%, and 34% respectively, compared with that of the LPS only group, without any cytotoxicity. The edema formation in the ICR mouse ear was also reduced compared to that in control. Moreover, there were no mortalities occurred in mice administered 5,000 mg/kg body weight of OPHWE. These results suggest that OPHWE has considerable anti-inflammatory activities and can be regarded as a potent candidate material to treat inflammatory diseases.

Activation of Intestinal Immune System by an Orally Administered Methanol Extract from Pine Needles (솔잎 메탄올추출물의 마우스 경구투여에 의한 장관면역 활성)

  • Yoon, Jin-A;Yu, Kwang-Won;Shin, Shun-Hyuck;Cho, Hong-Yeon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.3
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    • pp.356-362
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    • 2010
  • When pine (Pinus densiflora) needles were fractionated into cold water (PD-CW), hot water (PD-HW) and methanol extract (PD-M), PD-M showed potent simulating activity (1.19-fold of the saline control) for proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. MeOH extracts were prepared by homogenization, stirring or reflux to identify the method of methanol extraction, and MeOH extract by reflux method showed significantly highest intestinal immune system modulating activity (1.30-fold) in vitro. The intestinal immune system modulating effect of orally administered PD-M fractionated from pine needles also were studied in mice. Analyzing intestinal immune system modulating activity mediated Peyer's patch cells from C3H/He mice which had been fed with PD-M at different doses for 7 days, 1.0 g/kg of BW/day indicated that the bone marrow cells had proliferated (3.65-fold of 3% EtOH administered group). In addition, the amounts of IL-6 in the culture supernatant of Peyer's patch cells at 1.0 g/kg of BW/day were increased (1.13-fold) whereas the production of GM-CSF was not dose dependent. These results indicate that oral administration of PD-M enhances the secretion of hematopoietic growth factors such as GM-CSF and IL-6 from Peyer's patch cells, and these cytokines also act on modulator of bone marrow cell proliferation.