• Title/Summary/Keyword: IL-6 inhibitory activity

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Inhibitory Effect of Dioscorea Bulbifera MeOH Extract on Pro-inflammatory Mediator In Vitro and In Vivo (황약자(黃藥子) 메탄올 추출물의 염증억제 효과)

  • Jung, Ji-Yun;Lee, Jong-Rok;Byun, Sung-Hui;Jung, Ji-Wook;Kim, Yong-Han;Kim, Sang-Chan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.2
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    • pp.310-318
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    • 2010
  • Dioscorea bulbifera is one of the traditional medicinal herb. It commonly used in the treatment of hematemesis, epistaxis, tuberculous cervical lymphadenitis, laryngitis, acute infectious disease in East Asia. In the present study, we have demonstrated the anti-inflammatory effects of Dioscorea bulbifera MeOH extract (DBME) in macrophage cell line. To investigate mechanism of the anti-inflammatory activity, we examined the effects of the lipopolysaccaride (LPS)-induced production of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), pro-inflammatory cytokines and expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), p-inhibitory ${\kappa}B{\alpha}$ (p-$I{\kappa}B{\alpha}$), and nuclear factor-${\kappa}B$ (NF-${\kappa}B$) in a murine macrophage cell line RAW 264.7. The RAW 264.7 cells were cultured in DMEM + serum medium for 24 hrs. After serum starvation for 24 hrs, the cells were treated with DBME 0.03, 0.10, 0.30 mg/$m{\ell}$ for 1 h, followed by stimulation with LPS (1 ${\mu}g/m{\ell}$) for activation of immune response. After treatment, cell viability was measured by MTT assay, and NO production was monitored by measuring the nitrite content in culture medium. The protein band of iNOS, COX-2, p-$I{\kappa}B{\alpha}$, and NF-${\kappa}B$ was determined by immunoblot analysis and levels of cytokine were analyzed by sandwich immunoassays. There were three experimental groups: carrageenan, DBME 0.3, 1.0 g/kg. Rats were administrated either carrageenan (40% PEG) or carrageenan + DBME (0.3, 1.0 g/kg body weight) for 4 days (p.o.). To induce acute paw edema, rats were injected 1% carrageenan (100 ${\mu}{\ell}$/rat, dissolved in sterilized saline). The effect of DBME in the carrageenan-induced rat paw edema. As results, DBME has an inhibitory effect on the production of NO, PGE2, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 and on the expression of iNOS, COX-2, p-$I{\kappa}B{\alpha}$ and translocation of NF-${\kappa}B$ to nuclear from cytosol. In addition, DBME effectively inhibited the increases of paw edema induced by carrageenan treatment in vivo. These results suggest that DBME can inhibit production of pro-inflammatory mediators and might be a useful source for treatment of acute inflammatory disease.

Anti-inflammatory effects of fruit and leaf extracts of Lycium barbarum in lipopolysaccharide-stimulated RAW264.7 cells and animal model (염증유도 RAW264.7 세포와 동물모델에서 구기자와 구기엽의 항염 효능)

  • Bae, Su-Mi;Kim, Ji-Eun;Bae, Eun-Young;Kim, Kyung-Ah;Ly, Sun Yung
    • Journal of Nutrition and Health
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    • v.52 no.2
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    • pp.129-138
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    • 2019
  • Purpose: Medicinal herbs have recently attracted attention as health beneficial foods and source materials for drug development. Recent studies have demonstrated that extracts of Lycium's fruits and roots have a range of physiologically active substances. The extract of Lycium's leaves has been reported to have excellent anti-oxidant and anti-microbial activity, but its anti-inflammatory efficacy is not known. The chlorophyll present in the leaves can act as an anti-oxidant or pro-oxidant depending on the presence of light. Therefore, this study analyzed the anti-inflammatory effects of Lycium's fruit extract (LFE), leaf extract (LLE), and leaf extract with chlorophyll removal (LLE with CR). Methods: This study examined the inhibitory effects of LFE, LLE, and LLE with CR on pro-inflammatory mediator production as well as on the expression of iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BALB/c mice. Results: LFE, LLE, and LLE with CR inhibited the production of pro-inflammatory mediators (NO, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) and the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Furthermore, the administration of LLE and LLE with CR inhibited the serum pro-inflammatory cytokine levels and suppressed DNA damage in BALB/c mice. In particular, LLE with CR exhibited the highest anti-inflammatory activity. Conclusion: These results suggest that the fruit and leaves of Lycium are potential therapeutic agents against inflammation.

Anti-inflammatory Effect of an Ethyl Acetate Fraction from Myagropsis yendoi on Lipopolysaccharides-stimulated RAW 264.7 Cells (LPS로 유도된 RAW 264.7 대식세포에 대한 애기외톨개 모자반(Myagropsis yendoi) 에틸아세테이트 분획물의 항염증 효과)

  • Kim, Bowoon;Kim, Jae-Il;Kim, Hyeung-Rak;Byun, Dae-Seok
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.47 no.5
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    • pp.527-536
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    • 2014
  • An ethanolic extract from Myagropsis yendoi was fractionated using several solvents. Among these, an ethyl acetate fraction (Myagropsis yendoi ethyl acetate fraction: MYE) showed the highest anti-inflammatory activity based on inhibition of lipopolysaccharides (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. We thus investigated the molecular mechanisms underlying MYE's inhibitory effects. Pretreatment of cells with up to $30{\mu}g/mL$ of MYE significantly inhibited NO production and inducible nitric oxide synthase expression in a dose-dependent manner (P<0.05). Similarly, MYE markedly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$, as well as their mRNA levels. While the nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) was strongly suppressed by MYE, the activation of a nuclear factor erythroid 2-related factor (Nrf2) was increased. Moreover, MYE significantly reduced the phosphorylation of JNK, p38 MAPK, and phosphatidylinositol 3-kinase/Akt in LPS-stimulated cells. These results indicate that MYE contains anti-inflammatory compounds, and that it might be used as a dietary supplement for the prevention of inflammatory diseases.

Effect of Inhibition Macrophage Migration Inhibitory Factor Activation by Hominis Placenta Herbal Acupuncture on Rheumatic Arthritis (자하차약침(紫河車藥鍼)의 MIF 활성 억제를 통한 LPS 유발 류마티스성 관절염의 치료 효과)

  • Hwang, Ji-Hye;Cho, Hyun-Seok;Lee, Hyun-Jin;Lee, Dong-Gun;Jeong, Won-Je;Jung, Chan-Yung;Kim, Kyung-Ho
    • Journal of Acupuncture Research
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    • v.25 no.3
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    • pp.41-51
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    • 2008
  • Objectives : This study is to evaluate Effect of Inhibition Macrophage Migration Inhibitory Factor(MIF) activation by Hominis Placenta Herbal Acupuncture(HPA) on Rheumatic Arthritis(RA). Hominis Placenta is the placenta of healthy human, which is vital-strengthening medical stuff. In recent years, Hominis Placenta applied to chronic diseases because it makes us more resistance to diseases. Therefore it is supposed that HPA is effective on RA, a kind of autoimmune disease. When RA is induced, MIF is activated, too. MIF affects the process of inflammatory disease including RA. Methods : In order to investigate the effect of Hominis Placenta extraction on MIF(early RA inducing cytokine) and MMP(Matrix Metallo Proteinase)-9 mRNA expression by means of Reverse Transcriptase- Polymerase Chain Reaction(RT-PCR). In this study, we investigated the effect of Hominis Placenta extraction on MIF(early RA inducing cytokine) and MMP-9 mRNA expression by means of RT-PCR. Besides we investigated changing of MIF in synovial membrane and, Interleukin-6 receptor(IL-6R)-$\alpha$(pro-inflammatory cytokine), Signal transducers and activators of transcription(STAT)-3, MMP-9 after treating mouse, which is artificially attacked with RA, with HPA on its $ST_{35}$, LE201 in vivo. Results : 1. As a result of treating Lipopolysaccharide(LPS)-stimulated Raw246.7cell with HPA, MIF(RA related cytokine) and MMP-9 mRNA expression is reduced in vitro. And this reaction is concentration-dependatant. 2. In synovial membrane of the mice treated with HPA, inhibition of MIF, IL-6R-$\alpha$, STAT3 & MMP-9 activation is observed in vivo. Conclusions : From the above results, it might be suggested that HPA mitigate tissue damage originated from RA, because it intercepts the early process of by inhibition MIF activity.

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Antimicrobial Effect on the Periodontal Pathogens and Anti-inflammatory Effect of Artemisiae Iwayomogii Herba (한인진(韓茵蔯)의 치주염세균에 대한 항균효과 및 항염효가)

  • Kim, Young-Hong;Jeong, Mi-Young;Lee, Na-Kyung;Lee, Jin-Yong;Herr, Yeek;Lee, Je-Hyun;Lim, Sabina
    • The Korea Journal of Herbology
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    • v.23 no.2
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    • pp.1-8
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    • 2008
  • Objectives : The purpose of this study was to evaluate on the antimicrobial effect on the periodontal pathogens and anti-inflammatory effect of Artemisiae Iwayomogii Herba. Artemisiae Iwayomogii Herba has been used for treating as Artemisiae Capilaris Herba in Korea. Methods : Artemisiae Iwayomogii Herba was prepared by extracting medicinal herb with water. We investigated antimicrobial activity by the minimun inhibitory concentration (MIC) test. We also investigated inhibition of IL-$1{\beta}$-induced collagenase-l(MMP-l), stromelysin-1(MMP-3), interleukin-6 gene expression in human gingival fibroblasts. Results : The antimicrobial effect of Artemisiae Iwayomogii Herba was evaluated with MIC against periodontopathogens; Porphyromonas gingivalis 2561, W50, A7A1-28, 9-14K-1, Prevotella intermedia28, and Actinobacillus actinomycetemcomitans Y4, MICs of Artemisiae Iwayomogii Herba were 0.156 mg/ml, 0.625 mg/ml, 0.313 mg/ml, 1.25 mg/ml, 10 mg/ml and 10 mg/ml. The anti-inflammatory effect of Artemisiae Iwayomogii Herba was evaluated with Influence of herbs on the IL-$1{\beta}$-induced expression of MMP-1, MMP-3, interleukin-6, IL-$1{\beta}$ increased MMP-1, MMP-3, interleukin-6 mRNA levels. Artemisiae Iwayomogii Herba significantly inhibited IL-$1{\beta}$-induced MMP-1, MMP-3, interleukin-6 gene expressions in a dose-dependent manner. Conclusions : These results suggested that Artemisiae Iwayomogii Herba might reduce the excessive proteolytic capacity of the gingival fibroblast during inflammation and could be developed a new drug in periodontitis.

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Effects of Kyejiinsam-tang in MIA-Induced Osteoarthritis Rats (계지인삼탕(桂枝人蔘湯)이 MIA로 유도된 골관절염 유발 Rat에 미치는 영향)

  • An, Soon-Sun;Heo, Dong-Seok
    • The Journal of Korean Medicine
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    • v.34 no.3
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    • pp.69-85
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    • 2013
  • Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

Antimicrobial Effect on the Periodontal Pathogens and Anti-inflammatory Effect of Eriobotryae Folium (비파엽(枇杷葉)의 치주염세균에 대한 항균효과 및 항염효과)

  • Jeong, Mi-Young;Kim, Young-Hong;Lee, Na-Kyung;Lee, Jin-Yong;Herr, Yeek;Lee, Je-Hyun;Lim, Sa-Bi-Na
    • The Journal of Korean Medicine
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    • v.29 no.2
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    • pp.182-192
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    • 2008
  • Objective: The purpose of this study was to evaluate on the antimicrobial effect on the periodontal pathogens and anti-inflammatory effect of Eriobotryae folium. Eriobotryae folium are constituent herbs of Gagamgamroum, which has been used for a long time in oriental medicine as a herbal medicine for treating halitosis and toothache. Method: Eriobotryae folium was prepared by extracting medicinal herb with water. We investigated antimicrobial activity by the minimum inhibitory concentration (MIC) test. We also investigated inhibition of $IL-1{\beta}-induced$ collagenase (mmp-1), stromelysin-1 (mmp-3), interleukin-6 gene expression in human gingival fibroblasts using RTPCR analysis. Result: The antimicrobial effects of Eriobotryae folium was evaluated with MIC against periodontopathogens; Porphyromonas gingivalis 2561, W50, A7A1-28, 9-14K-1, Prevotella intermedia 28, and Actinobacillus actinomycetemcomitans Y4. MICs of Eriobotryae folium were 1.25 mg/ml, 2.5 mg/ml, 0.625 mg/ml, 1.25 mg/ml, 10 mg/ml and 10 mg/ml. The anti-inflammatory effect of Eriobotryae folium was evaluated with influence of herbs on the $IL-1{\beta}-induced$ expression of mmp-1, mmp-3, and interleukin-6. $IL-1{\beta}$ increased mmp-1, mmp-3, and interleukin-6 mRNA levels. Eriobotryae folium significantly inhibited $IL-1{\beta}-induced$ mmp-1, mmp-3, and interleukin-6 gene expressions in a dose-dependent manner. Conclusion: These results suggested that Eriobotryae folium might reduce the excessive proteolytic capacity of the gingival fibroblast during inflammation and could be developed as a new drug for periodontitis.

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Anti-inflammatory Activity of Stevia rebaudiana in LPS-induced RAW 264.7 Cells

  • Jeong, Il-Yun;Lee, Hyo-Jung;Jin, Chang-Hyun;Park, Yong-Dae;Choi, Dae-Seong;Kang, Min-Ah
    • Preventive Nutrition and Food Science
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    • v.15 no.1
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    • pp.14-18
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    • 2010
  • Stevia rebaudiana (SR) is an herb used traditionally as a sweetener in Paraguay and Brazil, whose use is spreading to other countries, such as Japan, Korea and China. In addition to its low calorie sweet taste, SR appears to have other beneficial properties, such as hypotensive capabilities and inflammation reduction. To identify the bioactive natural constituents exerting anti-inflammatory activities, we examined the EtOAc fraction of SR. In the inflammatory mediator inhibitory assay from lipopolysaccharide (LPS)-activated macrophages, the EtOAc fraction significantly, and dose dependently, inhibited the enhanced production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression. We also found that treatment of cells with the EtOAc fraction significantly inhibited LPS-stimulated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) reporter gene expression. Such inhibition of NF-${\kappa}B$ was closely associated with the inhibition of interleukin-6 (IL-6) and the monocyte chemoattractant protein-1 (MCP-1). Therefore, we suggest that SR has the potential for development as a functional food for the treatment of immune diseases, such as rheumatoid arthritis and lupus.

Synthesis and SAR of N-Chlorophenyl Substituted Piperrazinylethyl-aminomethylpyrazoles as 5-HT3A Inhibitors

  • Lee, Byung-Hwan;Choi, In-Sung;Rhim, Hye-Whon;Choi, Kyung-Il;Nah, Seung-Yeol;Nam, Ghil-Soo
    • Bulletin of the Korean Chemical Society
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    • v.30 no.11
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    • pp.2707-2712
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    • 2009
  • 5-$HT_{3}$ receptor;5-$HT_{3A}$ receptor channel activity;Novel 5-$HT_{3}$ receptor channel current blockers;Chlorophenyl substituted piperazinylethylaminomethylpyrazoles; The 5-$HT_{3A}$ receptors are one of ligand-gated ion channels and are known to be involved in visceral pain, anxiety, or anticancer agent-induced nausea and vomiting. In present study, we designed novel skeletons based on the developed 5-$HT_{3}$ receptor antagonists and evaluated their effects on 5-$HT_{3A}$ receptor channel currents ($I_{5-HT}$) of a series of pyrazole derivatives having N-chlorophenylpiperazine functionality (6-9). We found that most of N-p-chlorophenyl substituted piperazinyl-pyrazole derivatives (7b, 7c, 7e and 7h) exhibited the high potency for the inhibition of $I_{5-HT}$, whereas the compound without chloride (6) or with m-chlorophenyl group (a serious of 8 and 9) showed the low potency. These result indicate that p-chlorophenyl group is might play an important role for increasing the inhibitory potency on $I_{5-HT}$.

Comparative Study of the Biological Activity Effects of Manjakani (Quercus infectoria Olivier) Extract using Water and 80% Ethanol (열수 및 80% 에탄올로 추출한 만자카니(Quercus infectoria Olivier)의 생리활성 비교연구)

  • Lee, Hea-Jin;Kim, Dong-Han;Lee, Eun-Jin;Lim, Mi-Hye
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.1
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    • pp.124-132
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    • 2020
  • The purpose of this study was to investigate the biological activities such as cytotoxicity and anti-inflammation using Manjakani (Quercus infectoria Olivier) extract. Manjakani was extracted from hot DW and 80% ethanol. Cell viability was assessed using MTT assay on RAW 264.7 cells. Also, anti-inflammatory activities were measured through changes in the levels of nitric oxide (NO), prostaglandin E2 (PGE2), leukotrien B4 (LTB4), pro-inflammatory cytokines (IL-1β, IL-6 and tumor necrosis factor (TNF)-α) and transcription factor on LPS-induced RAW264.7 cells. The results confirmed that significant cytotoxicity does not appear in the concentration range of 1, 5, and 10 ㎍/㎖ of both extracts of this study. The production of NO was slowed by approximately MDE 37.2% and MEE 43.7% at 10 ㎍/㎖ concentration. Also, level of PGE2 and LTB4 was decreased MDE 30.9%/MEE 43.7% and MDE 37.1%/MEE 43.7%. In the case of inflammatory cytokine was reduced to MDE 38.8%/MEE 50.8% for IL-1β, MDE 35.0%/MEE 44.2% for IL-6 and MDE 31.9%/MEE 36.6% for TNF-α at 10 ㎍/㎖ concentration. The mRNA expression of NF-κB, iNOS and COX-2 significantly decreased by MDE 44.0%/MEE 16.0%, MDE 44.0%/MEE 55.0% and MDE 45.0%/MEE 40.0%, respectively, following the 10 ㎍/mL sample treatment when compared to the control. Both extracts were effective in anti-inflammatory activity. In addition, both extracts showed efficient changes of production of NO, PGE2, LTB4, pro-inflammatory cytokines and transcription factor. But MEE was found to have a higher inhibitory effect than MDE. In other words, Manjakani was showed significant biological activities showing anti-inflammation without cytotoxicity. These results will be provided as fundamental data for further development of the new health food and therapeutics related to the results above.