• Title/Summary/Keyword: NF-${\kappa}B$ inhibitory activity

Search Result 168, Processing Time 0.028 seconds

Therapeutic Potential of Ethanolic Extract of Ecklonia cava on Inhibition of Inflammation

  • Kim, Moon-Moo;Lee, Sang-Hoon;Ngo, Dai-Nghiep;Jung, Won-Kyo;Kim, Se-Kwon
    • Journal of Marine Bioscience and Biotechnology
    • /
    • v.2 no.2
    • /
    • pp.86-93
    • /
    • 2007
  • Chronic inflammation has been known to have a close relationship with several diseases including periodontitis, colitis, hepatitis and arthritis. Recently anti-inflammatory agents have been developed from marine natural resources. In this study, Ecklonia cava (EC) was found to have anti-inflammatory effect. Ethanolic extract of EC belonging to brown algae exhibited an excellent inhibitory effect on the production of inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6 and prostaglandin $E_2$ by RA W264.7 cells. Furthermore, in reporter gene assay and western blot analysis, EC extract exerted anti-inflammatory effect via inactivation of NF-${\kappa}B$ transcription factor that regulates the expression of these inflammatory mediators in macrophages. In addition, EC extract inhibited the activity of matrix metalloproteinase that play an important role in chronic inflammation. These results suggest that EC extract may provide a pharmaceutical potential in inhibiting chronic inflammation.

  • PDF

Inhibitory Effect of NAD(P)H:Quinone Oxidoreductase 1 on the Activation of Macrophages (NQO1 (NAD(P)H:quinone oxidoreductase 1)에 의한 대식세포 활성화 억제)

  • Hong, Ji;Zhang, Peng;Yoon, I Na;Kim, Ho
    • Journal of Life Science
    • /
    • v.27 no.8
    • /
    • pp.873-878
    • /
    • 2017
  • We previously reported that NAD(P)H:quinone oxidoreductase 1 (NQO1)-knockout (KO) mice exhibited spontaneous inflammation in the gut. We also found that NQO1-KO mice showed highly increased inflammatory responses compared with NQO1-WT control mice when subjected to DSS-induced experimental colitis. In a Clostridium difficile toxin-induced mouse enteritis model, NQO1-KO mice were also sensitive compared with NQO1-WT mice. Moreover, numerous studies have shown that NQO1 is functionally associated with immune regulation. Here, we assessed whether NQO1 defects can alter macrophage activation. We found that peritoneal macrophages isolated from NQO1-KO mice produced more IL-6 and $TNF-{\alpha}$ than those isolated from NQO1-WT mice. Moreover, the dicumarol-induced inhibition of NQO1 significantly increased IL-6 and $TNF-{\alpha}$ production in peritoneal macrophages isolated from NQO1-WT mice, as well as in the cultured mouse macrophage cell line, RAW264.7. These results indicate that NQO1 may negatively regulate the activation of macrophages. Knockout or chemical inhibition of NQO1 markedly reduced the expression of $I{\kappa}B$ (inhibitor of $NF{\kappa}B$) in both mouse peritoneal macrophages and RAW264.7 cells. Finally, RAW264.7 cells treated with dicumarol exhibited morphological changes reflecting macrophage activation. Our results suggest that NQO1 may suppress the $NF{\kappa}B$ pathways in macrophages, thereby suppressing the activation of these cells. Thus, immunosuppressive activity may be among the many possible functions of NQO1.

Inhibitory Effect of Sageretia theezans against the Production of Pro-Inflammatory Mediators through the Inhibition of NF-κB and MAPK, and Activation of Nrf2/HO-1 Signaling Pathways in LPS-Stimulated RAW264.7 cells

  • Kim, Ha Na;Park, Su Bin;Kim, Jeong Dong;Jeong, Hyung Jin;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
    • /
    • 2018.10a
    • /
    • pp.98-98
    • /
    • 2018
  • In this study, we evaluated the anti-inflammatory effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in LPS-stimulated RAW264.7 cells. ST-L and ST-B significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, $IL-1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. ST-L and ST-B blocked LPS-induced degradation of $I{\kappa}B-{\alpha}$ and nuclear accumulation of p65, which resulted to the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. ST-L and ST-B also attenuated the phosphorylation of ERK1/2, p38 and JNK in LPS-stimulated RAW264.7 cells. In addition, ST-L and ST-B increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of ST-L and ST-B against LPS-induced NO production in RAW264.7 cells. Inhibition of p38 activation and ROS elimination attenuated HO-1 expression by ST-L and ST-B, and ROS elimination inhibited p38 activation induced by ST-L and ST-B. ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing $NF-{\kappa}B$ and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

  • PDF

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
    • /
    • v.15 no.1
    • /
    • pp.14-18
    • /
    • 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.

Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes

  • Jo, Hyundong;Jang, Ha Young;Youn, Gi Soo;Kim, Donggyu;Lee, Chae Yeon;Jang, Jae Hee;Choi, Soo Young;Jun, Jong-Gab;Park, Jinseu
    • BMB Reports
    • /
    • v.51 no.8
    • /
    • pp.394-399
    • /
    • 2018
  • Human immunodeficiency virus-1 (HIV-1) transactivator of transcription (Tat) is an important viral factor in neuro-inflammation. Hindsiipropane B, present in Celastrus hindsii, possesses various biological mechanisms including anti-inflammatory activity. In this report, we explored the regulatory activity of hindsiipropane B on HIV-1 Tat-mediated chemokine production and its mode of action in astrocytes. Hindsiipropane B significantly alleviated HIV-1 Tat-mediated production of inflammatory chemokines, CCL2, CXCL8, and CXCL10. Hindsiipropane B inhibited expression of HDAC6, which is important regulator in HIV-1 Tat-mediated chemokine production. Hindsiipropane B diminished HIV-1 Tat-mediated reactive oxygen species (ROS) generation and NADPH oxidase activation/expression. Furthermore, hindsiipropane B inhibited HIV-1 Tat-mediated signaling cascades including MAPK, $NF-{\kappa}B$, and AP-1. These data suggest that hindsiipropane B exerts its inhibitory effects on HIV-1 Tat-mediated chemokine production via down-regulating the HDAC6-NADPH oxidaseMAPK-$NF-{\kappa}B$/AP-1 signaling axis, and could serve as a therapeutic lead compound against HIV-1 Tat-associated neuro-inflammation.

Inhibitory Effect of Persicaria perfoliata (L.) H. Gross on IgE Mediated Allergic Responses in RBL-2H3 Cells

  • Yoon, Hyun-Seo;Park, Chung-Mu
    • Journal of The Korean Society of Integrative Medicine
    • /
    • v.8 no.4
    • /
    • pp.163-169
    • /
    • 2020
  • Purpose : This study aimed to investigate the anti-allergic effect of Persicaria perfoliata water extract (PPWE) on IgE stimulated rat basophilic leukemia (RBL-2H3) cell line. Methods : P. perfoliata (L.) H. Gross has been used in traditional medicine as an anti-allergic agent, antipyretic, and diuretic and for respiratory disorders. To analyze the anti-allergic activity of PPWE, release of β-hexosaminidase in RBL-2H3 cells was estimated by enzyme linked immunosorbant assay (ELISA). Also, the cytotoxic effect of PPWE was identified by WST assay, and nuclear factor (NF)-κB and its upstream signaling molecules were assessed by western blot analysis. Results : PPWE treatment significantly attenuated β-hexosaminidase release in a dose dependent manner without any cytotoxicity. PPWE inhibited β-hexosaminidase activity by 38.4±1.2, 36.6±0.6, 32.5±2.2 and 26.5±1.2 at 500, 250, 100, and 50 ㎍/㎖ of PPWE, respectively, compared with the control group. In addition, an analysis of the expression level of NF-κB, an inflammation transcription factor, in RBL-2H3 cells upon IgE stimulation provided reults consistent with the results of β-hexosaminidase release. The phosphorylated status of upstream signaling molecules for transcription factor, mitogen activated protein kinases (MAPKs), was also analyzed. The results showed that PPWE treatment dose-dependently inhibited phosphorylation of extracellular regulatory kinase (ERK) and c-Jun N-terminal kinase (JNK). These results show that PPWE had a strong IgE-mediated degranulation inhibitory effect on RBL-2H3 cells. Conclusion : P. perfoliata ameliorated IgE-mediated allergic reaction via the modulation of MAPK and NF-κB signaling pathway in RBL-2H3 cells. These results indicate that P. perfoliata could be a potential candidate for a treatment strategy against various allergic disorders.

Doxorubicin Inhibits the Production of Nitric Oxide by Colorectal Cancer Cells

  • Jung, In-Duk;Lee, Jang-Soon;Yun, Seong-Young;Park, Chang-Gyo;Han, Jeung-Whan;Lee, Hyang-Woo;Lee, Hoi-Young
    • Archives of Pharmacal Research
    • /
    • v.25 no.5
    • /
    • pp.691-696
    • /
    • 2002
  • Doxorubicin (DOX) is an active and broad spectrum chemotherapeutic agent. Increased inducible nitric oxide synthase (NOS) expression and/or activity have been reported in several human tumors. While the relationship between DOX treatment and the enzymatic activity of endothelial NOS has been well characterized, little is known about the effects of DOX on the expression of iNOS in human cancer cells. In the present study, we characterized the effects of DOX on the nitric oxide (NO) production by colorectal cancer cells, DLD-1. IFN-${\gamma}$/IL-1$\beta$ (CM) increased the production of NO, whereas pretreatment of DOX inhibited the production of NO in response to CM in a dose dependent manner. The increased expressions of iNOS mRNA and protein by CM were completely blocked by DOX without affecting the iNOS mRNA stability. However, DOX activated nuclear factor-kB (NF-kB) in response to CM. Furthermore, the expression of inhibitor kB$\alpha$ was reduced by DOX in a dose dependent manner. Collectively, DOX inhibited the production of NO by DLD-1 cells, which is not linked to well known transcription factor, NF-kB. Therefore, further studies on the possible mechanisms of inhibitory effects of NO production by DOX would be worth pursuing.

Effects of Dendrobii herba and Punica granatum Extract on the Anti-oxidant, Anti-inflammatory, Anti-wrinkle and Whitening (석곡(石斛), 석류(石榴)의 항산화, 항염증, 주름, 미백에 미치는 영향)

  • HwangBo, Min;Roh, Seok-Sun;Seo, Hyeong-Sik
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
    • /
    • v.23 no.3
    • /
    • pp.11-32
    • /
    • 2010
  • Objective : The aim of this study is to determine the effects of Dendrobii herba extract and Punica granatum extract on skin disease and skin beauty. Methods : To investigate in vitro anti-oxidant activity assay, ethanol extracts of medicinal plants tested by DPPH radical, xanthine oxidase activity. In the next experiment, to investigate anti-inflammatory activity assay, examined by relations in NO synthesis, IL-$1{\beta}$, IL-6, TNF-${\alpha}$, NF-${\kappa}B$, COX-2, MAP kinase. To study Skin wrinkle formation effect, we were examined by tyrosinase activities, melanin synthesis in MNT-1 cell. Results : 1. In an anti-oxidant test, Dendrobii and Punica granatum extract showed high radical scavenging activity. 2. In an anti-inflammatory test, Dendrobii herba and Punica granatum extract weakly inhibited the lipopolysaccharide(LPS)-induced nitric oxide(NO) release from RAW 246.7 macrophage cells. Dendrobii herba and Punica granatum extract also inhibited LPS-induced IL-$1{\beta}$ and COX-2 expressions. The inhibitory effect of Dendrobii herba and Punica granatum extract on macrophage activation were via the inhibition of NF-${\kappa}B$, evidenced by transient transfection assay. however, Dendrobii herba and Punica granatum extract did not have any effects about activation of Jun-N-terminal kinase(JNK) and inhibition of p38 MAP kinase in RAW 264.7 cells. 3. In the skin wrinkle formation assay, Dendrobii herba and Punica granatum extract weakly inhibited collagenase and elastase, however it was not statistically significant. 4. In the skin whitening assay, Dendrobii herba and Punica granatum extract weakly inhibited tyrosinase activity, however, it was not statistically significant. They did not have any effect on melanin synthesis, indicating that they could not be applicable for skin whitening. Conclusion : Dendrobii herba extract and Punica granatum extract may play a significant role in skin disease and skin beauty.

Glycoprotein Isolated from Morus indica Linne Has an Antioxidative Activity and Inhibits Signal Factors Induced by Bisphenol A in Raw 264.7 Cells (뽕잎 당단백질의 항산화능과 Raw 264.7 세포에 있어서 bisphenol A에 유도된 신호전달인자의 억제)

  • Shim, Jae-Uoong;Lee, Sei-Jung;Oh, Phil-Sun;Lim, Kye-Taek
    • Korean Journal of Food Science and Technology
    • /
    • v.39 no.2
    • /
    • pp.209-216
    • /
    • 2007
  • The present study investigated anti-oxidative and anti-inflammatory activity of glycoprotein isolated from Morus Indica Linne (MIL glycoprotein). We found that MIL glycoprotein has a molecular weight of 32 kD and consists of carbohydrate (40.03%) and protein (59.97%), and that it has a strong scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical $({\cdot}OH)$, and superoxide anion $(O_2{\cdot}\;^-)$ radicals. In addition, MIL glycoprotein had a stable character and an optimal DPPH radical scavenging activity in the alkaline and neutral pH solution, and up to at 105. However, the results indicated that it has a minimal scavenging activity in the metal ionic solution ($Ca^{2+}$, $Mn^{2+}$, and $Mg^{2+}$) in the presence of EDTA. In addition, we further investigated whether MIL glycoprotein scavenges oxygen radicals and blocks inflammation-related signals in the bisphenol A (BPA)-stimulated Raw 264.7 cells. The results in this study showed that it has a character to scavenge the productions of reactive oxygen species (ROS) and nitric oxide (NO) dose-dependently. Also it blocked the activities of inflammation-related signals such as nuclear factor-kappa B ($NF-{\kappa}B$) and inducible nitric oxide synthase (iNOS). For example, it had an inhibitory effect on the activation of $NF-{\kappa}B$ (p50) and iNOS proteins at 200 ${\mu}g/mL$ MIL glycoprotein. Here, we speculate that MIL glycoprotein is one of natural antioxidants and of modulators of the BPA-induced inflammation.