• The Journal of the Society of Korean Medicine Diagnostics
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• v.17 no.3
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• pp.263-273
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• 2013

Objectives This study was designed to investigate the anti-inflammatory effect of extracts from Ligustrum obtusifolium S. fruits(LOF) in RAW 264.7 Macrophages stimulated with lipopolysaccharide(LPS). Methods We examined productions of nitric oxide(NO), reactive oxygen species(ROS), inducible isoforms of NO synthase(iNOS), cyclooxygenase-2(COX-2) to investigate the anti-inflammatory effect of LOF extracts. In addition, we measured generation of pro-inflammatory cytokines(TNF-${\alpha}$, IL-6). Results Cell viability showed that LOF extracts had no cytotoxicity in Raw 264.7 cells. The treatment with LOF extracts significantly decreased the generation of NO and pro-inflammatory cytokines(TNF-${\alpha}$, IL-6) in LPS-stimulated macrophage cells. Furthermore LOF extracts inhibited intracellular ROS generation dose dependently and reduced the expression of iNOS, COX-2 proteins. Conclusions These results showed that the LOF extracts had an anti-inflammatory effect on LPS-stimulated Raw 264.7 cells. These findings provide scientific support for the use of this Ligustrum obtusifolium S. for inflammatory-related diseases.

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.216-219
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• 2006

In order to establish the anti-inflammatory cellular mechanism of the paeony root(Paeonia lactiflora, Pall, Paeoniaceae), the constituents including paeoniflorin, albiflorin, (+)-catechin, paeonol, benzoic acid and methyl gallate were evaluated for their effects on arachidonate and NO metabolism. Among the compounds tested, only paeonol weakly inhibited cyclooxygenase-2-mediated $PGE_2$ production from LPS-treated RAW 264.7 cells. (+)-Catechin and methyl gallate weakly inhibited inducible nitric oxide synthase-mediated NO production from the same cell line. In particular, methyl gallate significantly inhibited 5-lipoxygenase from RBL-l cells with an $IC_{50}$ of 8.4 ${\mu}M$. These results suggest that the inhibition of these components on arachidonate and NO metabolism may contribute at least in part to anti-inflammatory mechanism of the paeony root.

• Journal of Trauma and Injury
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• v.18 no.1
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• pp.53-63
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• 2005

Purpose: This study was designed to determine if methylene blue inhibited the lipid peroxidation, the production of NO, and the gene expression of iNOS in acute lung injury induced by paraquat and if the inhibitory effect was dose dependent. Methods: Female Sprague-Dawley rats were divided into four groups: the control group, the group treated with paraquat only, the group treated with paraquat and a low dose of methylene blue (2 mg/kg), and the group treated with paraquat and a high dose of methylene blue (20 mg/kg). Methylene blue was administered via the jugular vein 1 h after paraquat administration, and animals were sacrificed 6 and 24 h after paraquat administration. Malondialdehyde (MDA) as lipid peroxidation, reduced glutathione (GSH) as an antioxidant defense, the plasma NO concentration, and the expression of iNOS mRNA in the lung tissue were measured Results: Lung MDA contents decreased, with no significant difference between the methylene-blue groups and the paraquat-only group. Lung GSH contents were significantly elevated at 24 h in the methylene-blue groups compared with the paraquat-only group. Plasma NO concentrations were significantly reduced at 6 and 24 h in the methylene-blue groups compared with the paraquat-only group. There was also a significant decrease in the plasma NO concentration at 6 h in the high-dose methylene-blue group compared with the low-dose methylene-blue group. The expression of iNOS mRNA in the lung tissue was slightly decreased in the methylene-blue groups. It was also markedly increased at 24 h in the paraquat-only group compared with the methylene-blue groups. The gene expression was relatively decreased in the high-dose methylene-blue group compared with the low-dose methylene-blue group. Conclusion: This study suggests that methylene blue has an inhibitory effect on the plasma NO concentration and the expression of iNOS mRNA in lung injury induced by paraquat. No inhibitory effect of methylene blue on lipid peroxidation or dose-dependent inhibitory effects were clearly shown.

• Molecules and Cells
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• v.23 no.3
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• pp.398-404
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• 2007

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in various pathophysiological processes such as inflammation and carcinogenesis. In a search for inhibitors of COX-2 and iNOS production we found that extracts of Stewartia koreana strongly inhibited NO and $PGE_2$ production in LPS-treated macrophage RAW 264.7 cells. We have now shown that the mRNA and protein levels of iNOS and COX-2 are reduced by the Stewartia koreana extract (SKE). SKE inhibited expression of an NF-${\kappa}B$ reporter gene in response to LPS, and gel mobility shift assays revealed that SKE reduced NF-${\kappa}B$ DNA-binding activity. The extract also inhibited LPS-induced phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Administration of the extract reduced the symptoms of arthritis in a collagen-induced arthritic mouse model. These results indicate that Stewartia extracts contain potentially useful agents for preventing and treating inflammatory diseases.

• Journal of Korean Medicine for Obesity Research
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• v.23 no.1
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• pp.1-9
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• 2023

Objectives: Noni fruit juice (NFJ) is liquor extracted from Morinda citrifolia (noni) fruit and has been used as an herbal remedy in many countries. However, the NFJ's anti-adipogenic and anti-inflammatory effects on adipocytes are poorly understood. The purpose of this study was to explore the commercially standardized NFJ effects on lipid accumulation throughout 3T3-L1 preadipocytes differentiation and interleukin-1β (IL-1β)-mediated inducible nitric oxide synthase (iNOS) expression in 3T3-L1 preadipocytes. Methods: Cellular lipid accumulation and triglyceride (TG) content in differentiating 3T3-L1 preadipocytes were assessed subsequently via the Oil Red O staining and AdipoRed assay. MTS assay was used to examine NFJ cytotoxicity in (differentiating) 3T3-L1 preadipocytes. Immunoblotting and reverse transcriptase polymerase chain reaction analysis were used to measure the expression levels of target protein and mRNA in (differentiating) 3T3-L1 preadipocytes, respectively. Results: NFJ treatment at 150 μL/mL led to a substantial reduction of fat accumulation and TG content during 3T3-L1 adipogenesis with no discernable impact on the cell viability. Of note, while NFJ treatment (150 μL/mL) largely inhibited the CCAAT/enhancer-binding protein-α (C/EBP-α) and peroxisome proliferator-activated receptor-β (PPAR-β) protein expressions, it did not influence PPAR-γ in differentiating 3T3-L1 preadipocytes. Of interest, treatment with IL-1β at 20 ng/mL for 4 hours elicited in firm induction of iNOS mRNA expression in 3T3-L1 preadipocytes. However, NFJ treatment at 100 or 200 μL/mL greatly attenuated the IL-1β-induced iNOS mRNA expression in 3T3-L1 preadipocytes. Conclusions: NFJ has anti-adipogenic and anti-inflammatory effects on (differentiating) 3T3-L1 preadipocytes which are in part intervened via control of the expression of C/EBP-α, PPAR-β, and iNOS.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1170-1176
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• 2005

2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphthoquinone[2,3-b]furan-4,9-dione (N FD-37) is a synthetic furonaphthoquinone compound. In this study, we determined that NFD-37 could inhibit the lipopolysaccharide (LPS)-induced production of inflammatory mediators in macrophages RAW 264.7. This compound inhibited LPS-induced nitric oxide (NO) or prostaglandin (PG) $E_{2}$ production in dose-dependent manners, with $IC_{50}$ values of 7.2 ${\mu}M$ and 5.3 ${\mu}m$, respectively. As the positive controls, pyrrolidine dithiocarbamate (30 ${\mu}M$) exhibited a $57{\%}$ inhibition of NO production, and NS-398 ($1{\mu}M$) manifested a $48{\%}$ inhibition of $PGE_2$ production. The inhibitory effects of NFD-37 on NO and $PGE_2$ production were determined to occur in conjunction with the suppression of inducible NO synthase or cyclooxygenase-2 expression. NFD-37 also inhibited the production of LPS-inducible tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6, at $IC_{50}$ values of 4.8-8.9 ${\mu}M$. We also determined the anti-inflammatory efficacy of NFD-37 using carrageenin-induced paw edema in experimental mice.

• Food Science and Biotechnology
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• v.18 no.4
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• pp.923-927
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• 2009

This study is to investigate the anti-inflammatory effects of the ethylacetate extract of Rehmannia glutinosa (RGEAE). The anti-inflammatory activities using nitric oxide (NO), cytokine, and chemokine production in lipopolysaccharide (LPS)-induced RAW 264.7 cells were checked. Results indicated that RGEAE suppressed the NO, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production in a dose-dependent manner. Inhibition of NO formation was due to a decrease in inducible NOS (iNOS) expression. It was also found that the anti-inflammatory activities of RGEAE resulted from its inhibitory role on the nuclear factor $(NF)-{\kappa}B$ activation and reactive oxygen species (ROS) production. Therefore, it is suggested that RGEAE has potential as a therapeutic material to attenuate the inflammatory disease such as rheumatoid arthritis.

• YAKHAK HOEJI
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• v.41 no.3
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• pp.365-369
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• 1997

Human chorionic gonadotropin (hCG) is a placental hormone and is involved in maintenance of the corpus luteum during pregnancy. In the present study, effect of hCG on nitiric ox ide (NO) generation from peritoneal macrophage was examined. hCG ahd no effect on NO generation by itself, whereas recombinant interferon- ${\gamma}$ (rIFN-${\gamma}$) alone had modest activity. When hCG was used in combination with rIFN-${\gamma}$, there was a marked cooperative induction of NO generation in a dose-dependent manner. The optimal effect of hCG on NO generation was shown at 6 hr after treatment with rIFN-${\gamma}$. Furthermore, northern blot analysis of showed that hCG increased the expression of inducible NO synthase(iNOS) gene. These results suggest that hCG induces NO generation from macrophages by increasing the expression of iNOS gene.

• Biomolecules & Therapeutics
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• v.10 no.4
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• pp.230-235
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• 2002

Gold sodium thiomalate (GST, gold compound) is a widely used anti-arthritic, anti-rheumatic and anti-inflammatory drug that is considered a good alternative to sodium salicylate (NaSA) for individuals who cannot tolerate salicylates. Nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation. Recent evidence suggests that anti-inflammatory effect of NaSA lies in the inhibition of iNOS, but nothing has been reported about the direct effect of iNOS expression by GST. The present study was designed to elucidate sequentially the action mechanisms of GST and NaSA on lipopolysaccharide (LPS) plus interferon-gamma (IFN-$\gamma$) induced iNOS expression in RAW 264.7 macrophages. Both GST and NaSA inhibited NO production and iNOS protein expression in a dose dependent manner. GST inhibited iNOS mRNA expression induced by LPS plus IFN-$\gamma$, whereas NaSA did not. These findings suggest that GST may exert anti-arthritic, anti-rheumatic and anti-inflammatory effect by inhibiting iNOS expression induced by LPS plus IFN-$\gamma$ at transcriptional level, whereas NaSA exert its effect by inhibiting iNOS expression at the translational or posttranslational level.

• Korean Journal of Pharmacognosy
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• v.38 no.2 s.149
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• pp.170-175
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• 2007

Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO$^-$), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. We tried to evaluate the effects of two kinds of varieties of Perilla frutescens var japnica Hara on the NO production in lipopolysaccharide (LPS)-activated microglia. The perilla cultivars of Namcheondeulkkae (NC) and Boradeulkkae (BR) were developed by pure line from the local variety and by a cross between 'deulkkae' and 'chajogi', respectively. Spirit, hexane, chloroform and butanol fractions of the leaves of NC and BR inhibited the production of NO in LPS-activated microglia. The fractions of BR showed stronger activity than NC and the spirit extracts was the most potent in both cultivars. The solvent fractions of BR suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells. Moreover, the extracts of NC and BR showed the activity of peroxynitrite scavenging in cell free bioassay system. These results imply that Namcheondeulkkae and Boradeulkkae might have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.