• Title/Summary/Keyword: $TNF-{\alpha}$ release

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Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway

  • Lee, Eunjung;Jeong, Ki-Woong;Shin, Areum;Jin, Bonghwan;Jnawali, Hum Nath;Jun, Bong-Hyun;Lee, Jee-Young;Heo, Yong-Seok;Kim, Yangmee
    • BMB Reports
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    • v.46 no.12
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    • pp.594-599
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    • 2013
  • The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-${\alpha}$, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signal-regulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, $8.79{\times}10^5M^{-1}$. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK.

Galgeun-tang, an Herbal Formula, Ameliorates Atopic Dermatitis Responses in Dust Mite Extract-treated NC/Nga Mice

  • Ha, Hyekyung;Lee, Jun Kyoung;Lee, Mee-Young;Lim, Hye-Sun;Shin, Hyeunkyoo
    • The Journal of Korean Medicine
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    • v.34 no.4
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    • pp.1-11
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    • 2013
  • Objectives: Galgeun-tang (GGT, gegen-tang, kakkon-to), an herbal formula, is used to treat the common cold, fevers, headaches, hangovers and neck and upper back stiffness. The drugs currently used to treat atopic dermatitis (AD) are limited by the significant adverse effects associated with their long-term usage. The need to efficiently manage the AD response while reducing side effects has led to the development of alternative remedies. Methods: To assess the effects of GGT on AD, the anti-inflammatory and anti-AD properties of GGT were evaluated in both in vitro and in vivo systems. Results: Nitric oxide (NO) and histamine production on lipopolysaccharide (LPS)-treated RAW264.7 cells and phorbol-12 myristate 13-acetate (PMA)/A23187-treated MC/9 cells, respectively, were inhibited by GGT. GGT reduced thymus and activation-regulated chemokine (TARC/CCL17) release on TNF-${\alpha}$/IFN-${\gamma}$ stimulated HaCaT cells in a dose-dependent manner. GGT reduced both plasma levels of IgE and histamine and the dermatitis score in house dust mite induced atopic dermatitis-like lesions on NC/Nga mice. However, there were no significant histopathological differences observed between the GGT group and the AD-induced group, such as AD-like lesions in the dorsal skin or ear or mast cell infiltration in the dorsal skin. Conclusions: These results indicate that GGT inhibits chemokine production by keratinocytes and the atopic dermatitis response in NC/Nga mice, suggesting that GGT may be useful as a therapeutic remedy for treating AD and allergic inflammation-related diseases.

Effects of Gagambojungikgi-tang on the Immune Mediators Regulation and Wound Healing in the rSj26 or Chemical Antigen induced Atopic Dermatitis Model Mice (rSj26 또는 화학 항원 유도 아토피 피부염 마우스 모델에서 가감보중익기탕의 면역 매개물 조절 및 상처치료 효과)

  • Heo, Jung-Hun;Song, Han-Na;Jang, Seon-Il
    • The Korea Journal of Herbology
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    • v.23 no.1
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    • pp.53-61
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    • 2008
  • Objectives : The aim of this study was to investigative the effects of Gagambojungikgi-tang (GBT), a Korean herbal medicine, on the immune mediators, T cell proliferation and wound healing in the recombinant Sj26 (rSj26) antigen induced atopic dermatitis(AD) model mice. Methods : GBT is the water extracts prepared from mixture of Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Atractylodes Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Artemisia iwayomogi Herba, Scutellaria Radix, Lonicera japonica Flos. This is a modified prescription of Bojungikgi-tang, which has been used for the treatment of indigestion, and immunological disease in east-asian countries. GBT was orally administered or externally applied at difference doses. The levels of immune mediators [(IgE, IgG1, prostaglandin E2 (PGE2), Th1/Th2 cytokines], T cell proliferation, and wound healing in the rSj26 or chemical antigen induced AD model BALB/c were investigated. Results : GBT dose-dependently suppressed the release of TNF-${\alpha}$, IL-$1{\beta}$ (Th1 cytokines), IL-4, IL-10 (Th2 cytokines), PGE2 (inflammatory mediators) and T cell proliferation. But GBT increased the production of IFN-${\gamma}$ (Th1 cytokine). Furthermore, A wound healing effect of GBT was similar to external application of dexamethasone. Conclusions : These results suggest that GBT suppresses the inflammatory mediators and regulates the Thl/Th2 cytokines, and promotes the wound healing. Therefore, these properties may contribute to the strong anti-AD effect of GBT.

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Effects of Sophorae Radix (SFR) on Allergic Inflammation related Atopy Dermatitis (고삼(苦蔘)이 알러지성 염증 반응에 미치는 영향)

  • Yu, Mao-Lun;Koo, Young-Sun;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.15 no.2
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    • pp.135-148
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    • 2006
  • Sophorae Radix (SFR) is known as a therapeutic drug that has been used in Oriental traditional medicine for the treatment of skin and mucosal ulcers, gastrointestinal hemorrhage, diarrhea, inflammation and arrhythmia. In the present study, we examined the effects of the aqueous extract of SFR on anti-inflammation, anti-allergic and anti-oxidant effect in various cell lines; they include mouse lung fibroblast cells (hFCs), human mast cells (HMC-1), human monocytic cells (THP-1), and RAW 264.7 cells. Treatment with SFR extract at a concentration of 250 ${\mu}g$/ml for 24h showed no significant decrease in the survival rate of the hFCs. SFR decreased the mRNA expression of IL-8, TNF-$\alpha$, and IL-6 in HMC-1 cells. SFR extract treatment significantly inhi-bited the protein expression of IL-6 and, IL-8 induced by mite in THP-1 cells and it also did MCP-1 expression. We examined the alternation of histamine release in HMC-1 cells for investigating anti-allergic effect of SFR. Histamine secretion decreased after the treatment with SFR. In addition, SFR extract treatment at a concentration of 10 ${\mu}g$/ml, 100 ${\mu}g$ /ml, and 200 ${\mu}g$/ml lowered the $\beta$-hexosaminidase to 10.3%, 21.7%, and 50.8%, respectively. IC50 of SFR extract in RBL-2H3 cells was 196.85 ${\mu}g$/ml. Both activity of NF-$\kappa$B promoter in RBL-2H3 cells significantly diminished after the dose-dependent treatment of SFR. Therefore, our results indicate that SFR has anti-inflammatory and it may be useful for treating allergic diseases such as atopic dermatitis.

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Anti-Anaphylactic Effects of Natural Extract Compounds(AllerQ) in the Rats (천연물 복합체가 추출물(알러큐)의 알러지 유발 흰쥐에 대한 항알러지 효과)

  • Suh Kyong-Suk;Kwon Myung-Sang;Cho Jung-Soon
    • Journal of the East Asian Society of Dietary Life
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    • v.14 no.5
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    • pp.425-437
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    • 2004
  • Medicinal plants are of great importance in providing healthcare to a large portion of the population in Korea. A number of plants are described in Dong-Ui-Bo-Gam for use in the treatment of allergic disorders, namely psoriasis, eczema, bronchial asthma, etc. In this study, we evaluated the effect of AllerQ, which is multi-complexes of various plants extracts such like Mori folium, Scutellaria baicallensis, Glycyrrhiza uralnsis, Mentha sacharinensis and Poncirus trifoliata on compound 48/80 induced anaphylactic shock, ovalbumin induced asthma in vivo and anti-IgE antibody induced hypersensitivity in vitro. We found antianaphylactic or antiallergic properties of AllerQ when given orally. AllerQ for prophylactic treatment for anaphylactic shocks have produced good results. AllerQ may modulate various aspects of immune function and allergic inflammation. In the present study, we analyse the effects of AllerQ on mast cell degranulation, mortality, cAMP/cGMP, O₂, H₂O₂ level, cyokine production and on the elicitation of IgE-mediated mast cell-dependent allergic inflammation in vivo and in vitro. We have established that AllerQ inhibited histamine release, cAMP/cGMP, O₂, H₂O₂ level, IL-4, tumor necrosis factor-alpha(TNF-α) and IL-6 production without having any significant physical change. These effects have been observed in mast cell(in vitro) and serum(in vivo) derived from three different origins that were activated by either immunological or non-immunological stimuli. These results suggest that the antianaphylactic and antiasthma tic action of AllerQ may be associated with an increase in the intracellular inhibition of the cAMP phosphodiesterase. Furthermore, AllerQ identified as potent inhibitors on O₂, H₂O₂ and cytokine activity. these data suggest that AllerQ may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as an useful functional food.

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Study on the Anti-microbacterial Activity, Anti-inflammatory and Anti-allergic Effects of Several Herb-Extract (수종의 한약 복합 추출물의 항균, 항염 및 항알레르기 효과에 대한 실험적 연구)

  • Kim Jin-Man;Oh Han-Cheol;Song Seong-Pil;Kim Nam-Kwen;Hwang Chung-Yeon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.103-114
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    • 2006
  • Herbal mixture water extract of (Chrysanthemum morifolium, Portulaca oleracea, Sanguisorba officinalis, Sophora flavescens, Phellodendron amurense, Cnidium monnieri) which exhibit several beneficial effects including acne and skin diseases, was tested for anti-microbial activity and anti-inflammation effects. The herbal mixture extract showed antimicrobial activity against Stapylococcus epidermis, and Propionibacterium acne. The growth of Stapylococcus epidermis, and Propionibacterium acne was inhibited completely by addition of 1.0% of the extract. Also in the present study we examined the mixture extract on compound 48/80 induced allergy and LPS induced cyclooxygenase-2(COX-2) gene expression in RAW 264.7 macrophage. The results indicated the ear swelling and histamine release induced by compound 48/80 were dose-dependently reduced, ranging 28-60%, and 48-72% , respectively. Furthermore the extract inhibited the expression of LPS-induced COX-2 proteins and mRNAs without an appreciable cytotoxic effects on RAW 264.7 cells. The LPS-induced cytokine gene expression including IL-$1{\beta}$, TNF-$\alpha$, and IL-6 were dose-dependently suppressed by the mixture extract. Based on these results, it is concluded that the herbal mixture water extract can be applied to the acne and skin diseases therapy.

The Immunomodulatory Activity of Mori folium, the Leaf of Morus alba L., in RAW 264.7 Macrophages in Vitro

  • Kwon, Da Hye;Cheon, Ji Min;Choi, Eun-Ok;Jeong, Jin Woo;Lee, Ki Won;Kim, Ki Young;Kim, Sung Goo;Kim, Suhkmann;Hong, Su Hyun;Park, Cheol;Hwang, Hye-Jin;Choi, Yung Hyun
    • Journal of Cancer Prevention
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    • v.21 no.3
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    • pp.144-151
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    • 2016
  • Background: Immunoregulatory elements have emerged as useful immunotherapeutic agents against cancer. In traditional medicine, Mori folium, the leaf of Morus alba L. (Moraceae), has been used for various medicinal purposes; however, the immunomodulatory effects have not been fully identified. We evaluated the immunoenhancing potential of water extract of Mori folium (WEMF) in murine RAW264.7 macrophages. Methods: RAW264.7 cells were treated with WEMF for 24 hours and cell viability was detected by an MTT method. Nitric oxide (NO) levels in the culture supernatants were assayed using Griess reagent. The productions of prostaglandin $E_2$ ($PGE_2$) and immune-related cytokines was measured using ELISA detection kits. The mRNA and protein expression levels of Inducible NO synthase, COX-2, and cytokines were assayed by reverse transcription-PCR and Western blotting, respectively. The effect of WEMF on phagocytic activity was measured using a Phagocytosis Assay Kit. Results: WEMF significantly stimulated the production of NO and $PGE_2$ as immune response parameters at noncytotoxic concentrations, which was associated with the increased expression of inducible NO synthase and COX-2. The release and expression of cytokines, such as $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6, and IL-10, were also significantly increased in response to treatment with WEMF. Moreover, WEMF promoted the macrophagic differentiation of RAW264.7 cells and the resulting phagocytosis activity. Conclusions: WEMF has the potential to modulate the immune function by regulating immunological parameters. Further studies are needed to identify the active compounds and to support the use of WEMF as an immune stimulant.

Effects of Aloe and Violae herba Extract on the Anti-oxidant, Anti-inflammatory, Anti-wrinkle and Whitening (노회(蘆薈)(알로에), 자화지정(紫花地丁)의 항산화, 항염증, 주름, 미백에 미치는 영향)

  • Kim, Chang-Hun;Jung, Hyeon-A;Roh, Seok-Sun;Hong, Seok-Hoon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.1
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    • pp.23-43
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    • 2010
  • Objective : This study was performed to assess the effects of Aloe and Violae herba extracts on skin disease and skin beauty. Methods : Anti-oxidant effects were measured by the scavenging for DPPH radical, xanthine oxidase activity. Anti-inflammatory effects were examined by relations in NO synthesis, IL-$1{\beta}$, IL-6, TNF-$\alpha$, NF-kB, COX-2, MAP kinase. The skin wrinkle formation effects were measured by collagenase and elastase activities. The whitening effects were examined by tyrosinase activities, melanin synthesis in MNT-1 cell. Results : 1. In an anti-oxidant test, Aloe and Violae herba extracts showed high radical scavenging activity. 2. In an anti-inflammatory test, Aloe and Violae herba extracts strongly inhibited the lipopolysaccharide(LPS)-induced nitric oxide(NO) release from the RAW 246.7 macrophage cells. Aloe and Violae herba extracts also inhibited the LPS-induced IL-$1{\beta}$ and COX-2 expressions. The inhibitory effects of Aloe and Violae herba extracts on macrophage activation were via the inhibition of NF-kB, evidenced by transient transfection assay. Furthermore, Aloe and Violae herba extracts weakly inhibited the activation of Jun-N-terminal kinase(JNK) but they did not have any effects on p38 MAP kinase in RAW 264.7 cells. 3. In the skin wrinkle formation assay, Aloe extract strongly inhibited collagenase and elastase, whose activity are tightly related with the wrinkle formation. 4. In the skin whitening assay, Aloe and Viloae herba extracts weakly inhibited tyrosinase activity, however, it was not statistically significant. Besides they did not have any effects on melanin synthesis, indicating that they could not be applicable for skin whitening. Conclusion : This study show that Aloe and Violae herba extracts may play a significant role in skin disease and skin beauty.

Nelumbo nucifera Leaves Inhibit HASMC Proliferation and Migration Activated by TNF-$\alpha$ (Human Aortic Smooth Muscle Cell에서 하엽(荷葉)의 항동맥경화 활성 연구)

  • Kim, Sun-Mo;Yun, Hyun-Jeong;Yi, Hyo-Seung;Won, Chan-Wook;Kim, Jai-Eun;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.24 no.4
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    • pp.77-86
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    • 2009
  • Objectives : The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Nelumbo nucifera leaves (NNL) on the proliferation and migration of HASMC. Additionally, the mechanisms involved in any observed effects were also evaluated. Methods : Apoptotic cells were measured by staining with FITC-labeled annexin V, followed by flow cytometric analysis. The expression level of apoptosis related proteins was confirmed by western blot. And MMP-9 activity was measured by gelatin zymography and MMP-9 expression was measured by ELISA Results : NNL completely inhibited the proliferation of HASMC via induction of the expression of apoptotic proteins including annexin V, cleaved poly ADP-ribose polymerase (PARP), and caspase-3 and -8. NNL treatment resulted in the release of cytochrome c into cytosol, a loss of mitochondrial membrane potential, a decrease in Bcl-2 and Bcl-xL and an increase in Bax expression. NNL also blocked HASMC migration via suppression of MMP-9. Conclusions : Taken together, these results indicate that NNL has the potential for use as an anti-artherosclerosis agent.

Effects of Achyranthes Bidentata Polysaccharide on Growth Performance, Immunological, Adrenal, and Somatotropic Responses of Weaned Pigs Challenged with Escherichia coli Lipopolysaccharide

  • Guo, Guanglun;Liu, Yulan;Fan, Wei;Han, Jie;Hou, Yongqing;Yin, Yulong;Zhu, Huiling;Ding, Binying;Shi, Junxia;Lu, Jing;Wang, Huirong;Chao, Jin;Qu, Yonghua
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.8
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    • pp.1189-1195
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    • 2008
  • A study was conducted with 48 weaned barrows ($28{\pm}3d$, $8.45{\pm}0.14kg$) to determine the effect of Achyranthes bidentata polysaccharide (ABPS) supplementation on pig performance, immunological, adrenal and somatotropic responses following Escherichia coli lipopolysaccharide (LPS) challenge. The experiment was a $2{\times}2$ factorial design; the main factors included diet (supplementation with 0 or 500 mg/kg ABPS) and immunological challenge (LPS or saline). On d 14 and 21 of the trial, pigs were given an intraperitoneal injection with either $100{\mu}g/kg$ BW of LPS or an equivalent amount of sterile saline. Blood samples were obtained 3 h after injection for analysis of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), prostaglandin $E_2$ ($PGE_2$), cortisol, growth hormone (GH), insulin-like growth factor (IGF)-I and immunoglobulin G (IgG). On d 2 after LPS challenge, peripheral blood lymphocyte proliferation (PBLP) was measured. LPS administration decreased average daily feed intake (ADFI) (p<0.05), had a tendency to decrease average daily gain (ADG) (p<0.10) during both the first and second challenge periods and increased (p<0.05) feed:gain ratio only during the first challenge period. ABPS tended to improve ADG (p<0.10) during the first challenge period, and improved ADG (p<0.05) and tended to improve ADFI (p<0.10) during the second challenge period. ABPS did not affect feed:gain ratio. An interaction (p<0.05) between LPS challenge and diet was observed for the plasma concentrations of TNF-${\alpha}$, $PGE_2$ and cortisol after both LPS challenges such that, among LPS-treated pigs, pigs fed the ABPS diet were lower for these indices than those receiving the control diet. In contrast, pigs fed the ABPS diet had higher IGF-I (p<0.05) compared with those fed the control diet. No effect of diet, LPS challenge or both on GH and IgG was observed after both LPS administrations. LPS challenge increased PBLP when these cells were incubated with $8{\mu}g/ml$ of LPS during both the challenge periods, and did likewise when incubated with $8{\mu}g/ml$ of concanavalin A only after the first challenge. ABPS had no effect on PBLP. These data demonstrate that ABPS alters the release of pro-inflammatory cytokines following an immunological challenge, which might enable pigs to achieve better performance.