• Title/Summary/Keyword: iNOS(inducible nitric oxide synthase)

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Anti-Inflammatory, Anti-Angiogenic and Anti-Nociceptive Activities of 4-Hydroxybenzaldehyde

  • Lim, Eun-Ju;Kang, Hyun-Jung;Jung, Hyun-Joo;Kim, Kyung-Hoon;Lim, Chang-Jin;Park, Eun-Hee
    • Biomolecules & Therapeutics
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    • v.16 no.3
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    • pp.231-236
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    • 2008
  • The current work was designed to assess novel pharmacological activities of 4-hydroxybenzaldehyde (HD), a major phenolic constituent of various natural products of plant origin, such as Gastrodia elata Blume. HD exhibited a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis. HD also displayed an inhibitory effect in acetic acid-induced permeability in mice. Anti-nociceptive activity of HD was convinced using the acetic acid-induced writhing test in mice. HD was able to suppress production of nitric oxide (NO) and induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. HD also diminished the reactive oxygen species (ROS) level elevated in the LPS-activated macrophages. In brief, HD exhibits anti-angiogenic, anti-inflammatory and anti-nociceptive activities possibly via down-regulating iNOS and/or COX-2, which may be partly responsible for pharmacological efficacies of various natural products.

In-vitro Anti-inflammatory Activity of Rubus coreanus Miq. on Nitric Oxide, $Interferon-\gamma$, Cycloxygenase-2, and Tumor Necrosis $Factor-\alpha$ Production in the Macrophage like Cell Line RAW 264.7 Activated by Lipopolysccharide

  • Choi, Se-Young;Lee, Kyou-Chae;Jeoung, Young-Jun;Lim, Beong-Ou
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.5
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    • pp.324-328
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    • 2007
  • To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $Interferon-{\gamma}\;(IFN-{\gamma})$ production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased $IFN-{\gamma}\;and\;TNF-{\alpha}$ production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

Suppressive effects on the expression of cyclooxygenase-2 and inducible nitric oxide synthase by a natural sesquiterpenoid in lipopolysaccharide-stimulated mouse macrophage cells

  • Min, Hye-Young;Park, Hyen-Joo;Park, Eun-Jung;Lee, Sang-Kook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.101-101
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    • 2003
  • Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

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Inhibition of the Induction of Nitric Oxide Synthase by Kobusin

  • Kim, Sang-Kyum;Pokharel, Yuba-Raj;Kim, Ok;Woo, Eun-Rhan;Kang, Keon-Wook
    • Toxicological Research
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    • v.23 no.2
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    • pp.123-126
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    • 2007
  • We isolated a lignan, kobusin from Geranium thunbergii and studied its effect on the expression of inducible nitric oxide synthase (iNOS) gene in a monocyte/macrophage cell line, RAW264.7 cells. Kobusin inhibited lipopolysaccharide (LPS)-stimulated NO production and the expression of iNOS in a concentration-dependent manner. To identify the mechanistic basis for its inhibition of iNOS induction, we examined the effect of kobusin on both the luciferase reporter activity using $NF-{\kappa}B$ minimal promoter and the nuclear translocation of p65. Kobusin suppressed the reporter gene activity and the LPS-induced movement of p65 in to nucleus. $NF-{\kappa}B$ activation is controlled by the phosphorylation and subsequent degradation of $I-{\kappa}B{\alpha}$, and in the present study, we found that $I-{\kappa}B{\alpha}$ phosphorylation was also inhibited by kobusin. Our findings indicate that kobusin may provide a developmental basis for an agent against inflammatory diseases.

The Effects of Aqueous Extracts of Aconiti ciliare tuber on Functional Recovery after Sciatic Crushed Nerve Injury in Rats

  • Cho, Tae-Young;Song, Yun-Kyung;Lim, Hyung-Ho
    • The Journal of Korean Medicine
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    • v.30 no.3
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    • pp.39-50
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    • 2009
  • Objective : The aim of this study was to evaluate the effects of Aconiti ciliare tuber on the descending pain and the recovery of locomotor function that results from sciatic crushed nerve injury in rats. Method : In order to assess the effects of the aqueous extract of Aconiti ciliare tuber on the recovery rate of locomotor function, we investigated the walking track analysis, and for the effects on the pain control we investigated brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) expression in the sciatic nerve and on the expressions of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region resulting from the sciatic crushed nerve injury in rats. Result : Treatment with Aconiti ciliare tuber significantly enhanced the SFIvalue, enhanced BDNF expression, decreased iNOS expression, and suppressed c-Fos expression. The present results showed that Aconiti ciliare tuber facilitated functional recovery following sciatic crushed nerve injury in rats. The recovery mechanisms of SFI by Aconiti ciliare tuber might be ascribed to the increase of BDNF expression for nerve regeneration and reinnervation and to the suppression of iNOS expression for inhibiting nerve inflammation. Conclusion : In this process it has been shown that Aconiti ciliare tuber can be used for pain control and functional recovery from peripheral nerve injury.

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Dendrobium moniliforme Stem Extract Inhibits Lipoteichoic Acid-Induced Inflammatory Responses by Upregulation of Heme Oxygenase-1

  • Lee, Young Ji;Kim, Ji-Hee;Kim, YoungHee
    • Journal of Microbiology and Biotechnology
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    • v.28 no.8
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    • pp.1310-1317
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    • 2018
  • The stems of Dendrobium moniliforme have been used in traditional herbal medicine for the treatment of fever and lack of body fluid in Korea. In this study, we investigated anti-inflammatory effects of the aqueous extract of D. moniliforme stems (DM) in response to lipoteichoic acid (LTA), a major constituent of the cell wall of Gram-positive bacteria. DM inhibited LTA-induced expression of a pro-inflammatory mediator inducible nitric oxide synthase (iNOS) in the murine macrophages. And DM induced expression of heme oxygenase-1 (HO-1) at the transcriptional level. Conversely, the knockdown of HO-1 expression by siRNA markedly reversed the inhibitory effects of DM on LTA-induced iNOS expression. We also demonstrated that nuclear translocation of Nrf2 was increased following treatment with DM. In addition, DM-mediated Nrf2 activation and HO-1 expression were suppressed by PI3K/Akt and p38 inhibitors; treatment with DM also resulted in phosphorylation of Akt and p38. These results suggest that DM inhibits the expression of iNOS in LTA-stimulated macrophages, and that these effects are mediated by the upregulation of HO-1 expression via PI3K/Akt/p38-Nrf2 signaling.

Curcumin Inhibits Ovalbumin-Induced Inducible Nitric Oxide Synthase Expression (Curcumin은 ovalbumin에 의해서 유도된 inducible nitric oxide synthase 억제)

  • Kim, Ji-Soo;Ahn, Hee-Jin;Shin, Hwa-Jeong;Gu, Gyo-Jeong;Eum, Sang-Hoon;Lee, Chung-Ho;Min, In-Soon;Youn, Hyung-Sun
    • Korean Journal of Food Science and Technology
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    • v.44 no.4
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    • pp.498-501
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    • 2012
  • Egg allergy has been reported as the most prevalent food hypersensitivity among children. One of the major egg allergens is ovalbumin (OVA). OVA is the major protein in the egg white, comprising 54% of its total protein content. Curcumin isolated from Curcuma longa has been used as folk remedies in order to treat many chronic diseases for many years. In the present report, we present biochemical evidence that curcumin inhibits the NF-${\kappa}B$ activation induced by OVA. Curcumin also inhibits OVA-induced iNOS expression and nitrite production. These data suggest new approaches for the development of efficient anti-allergic strategies.

Human placental extract suppresses lipopolysaccharide-induced expressions of cyclooxygenase-2 and inducible nitric oxide synthase in mouse BV2 microglial cells

  • Yang, Sang-Eun;Kim, Yong-Suk;Park, Dong-Suk
    • Journal of Acupuncture Research
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    • v.22 no.2
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    • pp.111-121
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    • 2005
  • Human placental extract (HPE), which is prepared from the placenta of healthy pregnant females, has been widely used in clinical field. HPE is known to possess anti-inflammatory, anti-viral, anti-oxidative, anti-mutagenic, and analgesic properties. In this study, the effect of HPE against lipopolysaccharide (LPS)-induced inflammation was investigated. From the present results, HPE was shown to suppress prostaglandin E2 synthesis (PGE2) and nitric oxide (NO) production by inhibition on the LPS-stimulated enhancement of the cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions in mouse BV2 microglial cells. These results suggest that HPE may offer a valuable mean of therapy for the treatment of brain inflammatory diseases by attenuating LPS-induced PGE2 and NO production.

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Induction of Nitric Oxide Production by Bafilomycin A1 in Mouse Leukemic Monocyte Cell Line

  • Hong, Jang-Ja;Nakano, Yasuhiro;Ohuchi, Kazuo;Kang, Young-Sook
    • Biomolecules & Therapeutics
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    • v.14 no.3
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    • pp.143-147
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    • 2006
  • In the mouse leukemic monocyte cell line RAW 264.7, the vacuolar-type $(H^+)$-ATPase (V-ATPase) inhibitor bafilomycin $A_1$ at 10 and 100 nM decreased cell growth and survival as determined by 3-(4,5-dimethyl(thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in a concentration-dependent manner. At such concentrations, bafilomycin $A_1$ induced nitric oxide (NO) production through the expression of inducible nitric oxide synthase (iNOS). The bafilomycin $A_1$-induced NO production was inhibited by the NOS inhibitor $N^G$-monomethyl-L-arginine acetate (L-NMMA). Our findings suggest that the V-ATPase inhibitor bafilomycin $A_1$ induces NO production through the expression of iNOS protein.