• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.425-430
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• 2011

In this study, we found that Forsythiae fructus (FF) and one of its main compounds, arctigenin, significantly inhibited nitric oxide production in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Arctigenin also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2, and inhibited the activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38. Moreover, it also reduced levels of proinflammatory cytokines, interleukin $1{\beta}$, tumor necrosis factor ${\alpha}$ and prostaglandin E2, and inhibited neuronal death in LPS-treated organotypic hippocampal cultures. Therefore, we suggest that arctigenin may confer a neuroprotective effect via the inhibition of neuroinflammation.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.381-385
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• 2019

We attempted to examine anti-inflammatory and anti-oxidant effects of 4'-O-${\beta}$-D-glucosyl-5-O-methylvisamminol (GOMV), the first epigenetic inhibitor of histone phosphorylation at Ser10. While GOMV did not affect the viability of murine macrophage RAW 264.7 cells, it significantly suppressed lipopolysaccharide (LPS)-induced generation of prostaglandin $E_2$ ($PGE_2$) and nitric oxide (NO) through transcriptional inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). GOMV also scavenged free radicals in vitro, increased NF-E2-related factor 2 (NRF2), and activated antioxidant response element (ARE), thereby resulting in the induction of phase II cytoprotective enzymes in human keratinocyte HaCaT cells. Finally, GOMV significantly protected HaCaT cells against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative intracellular damages. Together, our results illustrate that GOMV possesses anti-inflammatory and anti-oxidant activity.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.194.2-194.2
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• 2003

The inhibitors of prostaglandin biosynthesis and nitric oxide production by corresponding inducible isozyme have been considered as potential anti-inflammatory and cancer chemopreventive agents. In our continuous search for cancer chemopreventive agents from natural products, we have evaluated the inhibitory potential of PGE$_2$ and NO production in lipopolysaccharide (LPS)-induced mouse macrophage RAW 264.7 cells. As a result, pinosylvin (3,5-dihydroxy-trans-stilbene), a stilbenoid, mainly found from the heartwood and leaves of the Pinus sylvestris, showed potential inhibitory activity of LPS-induced PGE$_2$ and NO production in a dose-dependent manner. (omitted)

• Journal of Digital Convergence
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• v.13 no.12
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• pp.461-467
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• 2015

Saussurea lappa is known for a variety of physiological activities as a component but has not known to show the effect of the cellular signaling pathway. We investigated the anti-inflammatory effects by Saussurea lappa ethanol extract on the LPS(lipopolysaccharide) induced nitric oxide (NO) production by RAW 264.7 cell line. It shows the expressions of iNOS and COX-2 at the transcriptional level (RT-PCR). The Saussurea lappa ethanol extract showed transcriptional expression levels of pro-inflammatory cytokine TNF- and IL-$1{\beta}$ induced by LPS(lipolysaccharide) in RAW264.7 cell line. Saussurea lappa ethanol extract reduced the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the RNA levels in a concentration-dependent manner. The finding that ethanol extract of Saussurea lappa has an influence on NO (nitric oxide) homeostasis in the study of the action mechanism on the macrophage-mediated inflammatory reaction was considered in terms of convergence. And it is to provide an important basis for the prevention and treatment of inflammatory diseases in the future.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.72-77
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• 2002

The present study was examined the effects of Bojungchiseup-tang water extract on the renal expression of renal function regulatory proteins including aquaporin 2 (AQP 2), aquaporin 3 (AQP 3), Na, K-ATPase α1 subunit, endothelial nitric oxide synthase (ecNOS), and inducible nitric oxide synthase (iNOS) in rats. The renal expression of AQP 3 was attenuated in rats administered with Bojungchiseup-tang water extract without altered expression of AQP 2, while ecNOS was up-regualted. Oral administration of Bojungchiseup-tang water extract (40 ㎕/100 g) also attenuated the renal expression of Na, K-ATPase α1-subunit and iNOS protein. These results suggest that the diuretic and natriuretic effects of Bojungchiseup-tang maybe causely related with a decreased expression of AQP 3 and increased expression of ecNOS.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.908-913
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• 2004

Farfrae Flos has been clinically used for the treatment of asthma in traditional oriental medicine. There is lack of studies regarding the effects of Farfrae Flos on the immunological activities. The present study was conducted to evaluate the effect of Farfrae Flos on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, Farfrae Flos water extract inhibited nitric oxide production in a dose-dependent manner and abrogated inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Farfrae Flos water extract did not affect on cell viability. To investigate the mechanism by which Farfrae Flos water extract inhibits iNOS and COX-2 gene expression, we examined the on the phospholylation of inhibitor κBα and production of TNF-α, IL-1β and IL-6. Results provided evidence that Farfrae Flos inhibited the production of interleukin-1β (IL-1β) and the activation of phospholylation of inhibitor κBα in Raw 264.7 cells activated with LPS. These findings suggest that Farfrae Flos can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.1
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• pp.95-110
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• 2008

목 적 : 급성 및 만성 염증 질환은 iNOS에 의해서 생성된 과량의 NO와 관련이 있다. 따라서 이러한 질병 치료를 목적으로 NO 생성 억제물질 또는 iNOS 발현 차단물질을 개발할 가치가 있다. 본 연구는 대사 안정성을 개선시킨 dimethoxycurcumin (DiMC)이 활성화된 대식세포에서 NO 생성 및 iNOS 발현을 제어할 수 있는지 조사하였다. 방 법 : RAW264.7 세포를 DiMC (양쪽 방향성 고리에 각각 2개의 methoxy group을 가짐), curcumin (양쪽 방향성 고리에 각각 1개의 methoxy group을 가짐), bis-demethoxycurcumin (양쪽 방향성 고리에 methoxy group이 없음; BDMC) 및 tetrahydrocurcumin (양쪽 방향성 고리에 각각 1개의 methoxy group을 가지고 있지만 중앙 7개 탄소 사슬에 이중결합이 없음; THC)로 각각 전처리한 후에 LPS로 자극하였다. 이들 전처리 물질의 효과를 비교하기 위하여, NO 생성, iNOS 발현, NF-kB p65 인산화 및 p65 DNA-binding 활성을 조사하였다. 결 과 : DiMC, curcumin 및 BDMC는 NO 생성, iNOS 발현 및 NF-kB 활성을 억제하였으며, 그 세기에 있어서 DiMC가 가장 크게 관찰되었고 그 다음 curcumin 그리고 BDMC 순으로 관찰되었다. THC는 어떠한 활성도 보이지 못했다. 결 론 :DiMC는 NO 생성 억제, iNOS 발현 차단 및 NF-kB 비활성을 유도할 수 있음을 알 수 있었다. 이러한 효과는 연속된 이중결합 및 methoxy group의 증가와 관련이 있는 것으로 판단된다.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.209-214
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• 2004

Lead has long been considered as a toxic environmental pollutant that severely damages the central nervous system. In various neurogenerative diseases, actrocytes become activated by proinflammatory cytokines. In the present study, we investigated whether lead (Pb$^{2+}$) affects inducible nitric oxide synthase (iNOS) expression in activated glial cells. Rat primary glial cells were stimulated with lipopolysaccharide (LPS, 1 ${\mu}$g/ml) plus IFN$_{\gamma}$(100 U/ml). Pre-treatment of Pb$^{2+}$ increased nitric oxide (NO) production in LPS/IFN$_{\gamma}$-stimulated glial cells. Lead itself, however, suppressed the basal production of NO in control glial cells. Addition of the iNOS inhibitors L-NAME (1 mM) and L-NNA (800 ${\mu}$M) prevented the Pb$^{2+}$-induced increase in NO production. Western blot analysis showed that pre-treatment of Pb$^{2+}$ augmented LPS/IFN$_{\gamma}$-induced increase in iNOS immunoreactivity, which was well correlated with the increased NO production. In addition, pre-treatment of Pb$^{2+}$ synergistically increased the iNOS mRNA expression induced by LPS and IFN${\gamma}$. The present results indicate that lead intoxication adversely affect brain function by potentiating iNOS expression and NO production in activated glial cells observed in various neurodegenerative diseases.

• Preventive Nutrition and Food Science
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• v.12 no.2
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• pp.74-78
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• 2007

Fucoidan, that is high-molecular-weight sulfated polysaccharides extracted from brown seaweeds has been shown to elicit various biological activities. Here, we investigated the effects of fucoidan on cell proliferation and nitric oxide (NO) production in neuronal blastoma cell (SH-SY5Y). In the present study, we demonstrated that fucoidan treatment resulted in increase of cell proliferation and NO production. When cells were treated with amyloid-${\beta}$ (A${\beta}$) in the absence or presence of fucoidan, fucoidan recovered the cell viability decreased by A${\beta}$ peptides. To further determine whether nitric oxide synthase (NOS) is involved in proliferative effect of fucoidan, cells were treated with NOS inhibitors in the absence or presence of fucoidan. Selective constitutive nitric oxide synthase (cNOS) inhibitor, diphenylene iodonium chloride (DPI), caused a decrease of cell viability, whereas cell viability was increased by specific inducible nitric oxide synthase (iNOS) inhibitor, S-methylisothiourea (SMT), in the fucoidan-untreated cells. Treatment with fucoidan inhibited the cell viability decreased in DPI-exposed cells. In contrast, fucoidan had no effect on cell growth in SMT-treated cells, indicating that cNOS may not play a role in the proliferation of fucoidan-treated cells. The present data suggest that fucoidan has proliferative and neuroprotective effects and these effects may be associated with iNOS.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.390-399
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• 2014

Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.