• Archives of Pharmacal Research
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• 제28권3호
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• pp.297-304
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• 2005

Naturally occurring flavonoids are known to modulate various inflammatory and immune processes. Based on structural property, in this study, molecular mechanism of flavonoids in modulating nitric oxide (NO) production and its signaling pathway were investigated using lipopolysaccharide (LPS)-activated RAW264.7 cells. Although flavonol-typed flavonoids (kaempferol and quercetin) more potently scavenged reactivity of nitric oxide ($\cdot$NO) as well as peroxynitrite (ONOO$\kappa$) than isoflavones (genistein and genistin), kaempferol, quercetin and genistein showed a little difference in inhibition of both inducible NO synthase expression and NO production, with IC$_{50}$ values of 13.9, 20.1 and 26.8 $\mu$M. However, there was a striking pattern related to structural feature in modulation of LPS-mediated signaling pathways. Thus, flavonols only inhibited transcription factor AP-1 activation, whereas isoflavones suppressed the DNA binding activation of NF-$\kappa$B and C/EBP$\beta$. Therefore, these data suggest that structural feature may be linked to decide drugs target molecule in LPS-mediated signaling pathways, rather than its potency.

• Journal of Microbiology and Biotechnology
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• 제17권12호
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• pp.2042-2045
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• 2007

The effect of chitosan oligosaccharide (COS, 1 kDa${\gamma}$, 10 ng/ml IL-$1{\alpha}$, and 25 ng/ml TNF-${\alpha}$) in HT-29 cells. Inducible nitric oxide synthase (iNOS) expression induced by these cytokines was inhibited by COS. COS pretreatment inhibited the invasiveness of cytokines-treated HT-29 cells through Matrigel-coated membrane in a dose-dependent manner. COS also inhibited cytokines-induced matrix metalloproteinase (MMP)-2 activity. This study shows that proinflammatory cytokines induce NO production, iNOS expression, and invasiveness of human colorectal adenocarcinoma HT-29 cells. COS pretreatment inhibited cytokines-mediated NO production, iNOS expression, and invasiveness of HT-29 cells. These results provide sufficient information for the further development of COS as an antitumor metastatic agent for the treatment of colon cancer.

• Biomolecules & Therapeutics
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• 제21권5호
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• pp.364-370
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• 2013

Resveratrol (trans-3,4'-trihydroxystillbene), a naturally occurring polyphenolic antioxidant found in grapes and red wine, elicits diverse biochemical responses and demonstrates anti-aging, anti-inflammatory, and anti-proliferative effects in several cell types. Previously, resveratrol was shown to regulate differentiation and inflammation in rabbit articular chondrocytes, while the direct production of nitric oxide (NO) in these cells by treatment with the NO donor sodium nitroprusside (SNP) led to apoptosis. In this study, the effect of resveratrol on NO-induced apoptosis in rabbit articular chondrocytes was investigated. Resveratrol dramatically reduced NO-induced apoptosis in chondrocytes, as determined by phase-contrast microscopy, the MTT assay, FACS analysis, and DAPI staining. Treatment with resveratrol inhibited the SNP-induced expression of p53 and p21 and reduced the expression of procaspase-3 in chondrocytes, as detected by western blot analysis. SNP-induced degradation of I-kappa B alpha ($I{\kappa}B-{\alpha}$) was rescued by resveratrol treatment, and the SN50 peptide-mediated inhibition of NF-kappa B (NF-${\kappa}B$) activity potently blocked SNP-induced caspase-3 activation and apoptosis. Our results suggest that resveratrol inhibits NO-induced apoptosis through the NF-${\kappa}B$ pathway in articular chondrocytes.

• Journal of Microbiology and Biotechnology
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• 제30권4호
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• pp.490-496
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• 2020

Consumption of anti-inflammatory nutraceuticals may help treat or prevent inflammation-related illnesses such as diabetes, cardiovascular disease, and cancer. This study evaluated the effect of Croton hirtus L'Hér extract (CHE) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor kappa-B (NF-κB) signaling cascades. CHE significantly suppressed LPS-induced NO production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophages, although cyclooxygenase (COX)-2 expression was not affected. CHE also suppressed LPS-induced IκB kinase (IKK), IκB, and p65 phosphorylation in RAW264.7 cells. Western blot and immunofluorescence assays of cytosol and nuclear p65 and the catalytic subunit of NF-κB showed that CHE suppressed LPS-induced p65 translocation from the cytosol to the nucleus. CHE also suppressed LPS-induced Interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in RAW264.7 cells. These results suggest that CHE prevents NO-mediated inflammation by suppressing NF-κB and inflammatory cytokines.

• Food Science and Biotechnology
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• 제18권4호
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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.

• 동의생리병리학회지
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• 제20권2호
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• pp.414-419
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• 2006

Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of inflammation and osteoarthritis. And nitric oxide (NO) activated the MMPs responsible for PG degradation in articular chondrocytes. Therefore, we have studied the effects on anti-inflammation and analgesic by ethyl acetate fraction from 70% ethanol extract of Perilla Frutescens (EPF). EPF inhibited LPS plus inflammation-cytokines-induced proteoglycan (PG) degradation, matrix-metalloproteinase (MMP-2,9) expression in rabbit articular chondrocytes. Also, EPF have inhibitory effects on LPS or LPS plus inflammation cytokines-induced nitric oxide (NO) and PGE2 production in mouse macrophage andrabbit articular chondrocytes. These results suggest that EPF decreases PGE2, iNOS, MMPs activity and PG degradation in mouse macrophage and/or rabbit articular chondrocytes. In vivo, EPF was shown to have inhibitory effects on acetic acid-induced pain. The herbal extract with this profile, may have utility in the treatment of osteoarthritis.

• 한국응용과학기술학회지
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• 제36권1호
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• pp.13-22
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• 2019

울금(Curcuma longa L.)의 산화억제 및 질소산화물 소거활성 등 기능성 소재로서 활용 가능성을 검토한 결과, 프로안토시아니딘(proanthocyanidin) 함량은 $69.000{\pm}2.737mg$ catechin equivalents (CE)/g dry weight으로 확인되었으며, 증류수(distilled water, DW), 70% 에탄올 및 노르말 부탄올(n-butanol)의 3가지 용매를 사용한 추출 수율은 DW (17.11%), 70% 에탄올(15.26%), 노르말 부탄올(4.12%) 순으로 관찰되었다. 총 플라보노이드(total flavonoid) 함량은 DW, 70% 에탄올 및 노르말 부탄올에서 각각 0.032, 0.512 및 2.221 mg quercetin equivalents (QE)/g의 함량으로 나타났고, 노르말 부탄올에서는 유의적인 차이를 보이며 높게 관찰되었다(p<0.05). Nitric oxide (NO) 라디칼 소거 활성은 농도 별(0.2~0.8 mg/mL) DW에서 15.64~26.20%, 70% 에탄올 10.52~20.76%, 노르말 부탄올에서 13.39~69.92%로 확인되었다. Nitrite ($NO_2$) 소거활성은 DW 및 70% 에탄올과 비교하였을 때 노르말 부탄올에서 강한 $NO_2$ 소거활성을 보였다. ${\beta}$-carotene 탈색 저해활성은 DW에서 8.81~25.93%, 70% 에탄올 1.20~20.20%, 노르말 부탄올 12.08~43.93%로 나타났다. 지질과산화 저해활성은 DW, 70% 에탄올 및 노르말 부탄올에서 각각 5.60~27.54%, 37.78~50.79% 및 41.79~46.39%로 동정되었다. 이에, 천연 항산화제 등 기능성 소재로서의 활용 가능성이 있을 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제10권4호
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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.

• Molecules and Cells
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• 제21권3호
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• pp.337-342
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• 2006

Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous depolarization (pacemaker potentials) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of vasoactive intestinal polypeptide (VIP) on the pacemaker potentials in cultured ICCs from murine small intestine were investigated by whole-cell patch-clamp techniques. Addition of VIP (50 nM-$1{\mu}M$) decreased the amplitude of pacemaker potentials and depolarized resting membrane potentials. To examine the type of receptors involved in ICC, we examined the effects of the $VIP_1$ agonist and found that it had no effect on pacemaker potentials. Pretreatment with $VIP_1$ antagonist ($1{\mu}M$) for 10 min also did not block the VIP (50 nM)-induced effects. On the other hand exposure to 1H-(1,2,4)oxadiazolo(4,3-A)quinoxalin-1-one (ODQ, $100{\mu}M$), an inhibitor of guanylate cyclase, prevented VIP inhibition of pacemaker potentials. Similarly KT-5823 ($1{\mu}M$) or RP-8-CPT-cGMPS ($10{\mu}M$), inhibitors of protein kinase G (PKG) blocked the effect of VIP (50 nM) on pacemaker potentials as did N-nitro-L-arginine (L-NA, $100{\mu}M$), a non-selective nitric oxide synthase (NOS) inhibitor. These results imply that the inhibition of pacemaker activity by VIP depends on the NO-cGMP-PKG pathway.

• Journal of Acupuncture Research
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• 제23권6호
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• pp.103-115
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• 2006

Objectives : Rheumatoid arthritis(RA) is a systemic & a chronic inflammatory autoimmune disease . A chronic , locally destructive inflammmatory reaction in human is examplified by the synovitis present in some connective tissue disorder. The presence of a number of cytokines, $TNF-{\alpha}$, iNOS & expression of nitric oxide, NF-kB p65 activation implies an important role of cellular immune response in RA inflammatory reaction. This study was designed to evaluate on the effects of the Homnis Placenta herbal acupuncture on EX-LE201 & ST 35 reducing expression of LPS-induced arthritis model in mice. Materials and Methods : Homnis Placenta herbal acupuncture was inserted into 10 rats induced rheumatoid arthritis. The acupunctures were injected into the EX-LE201 and ST35 points. Such indexes were measured the inhibition of inducible nitric oxide synthase(iNOS) expression, nitric oxide(NO) production in vitro experiment and Tumor Necrosis $Factor-{\alpha}(TNF-{\alpha})$ & Nuclear Factor kappa $B(NF-{\kappa}B)$ p65 activation, synovial hyperplasia, angiogenesis and fibrosis in synovial membrane of knee joint of mice in vivo experiment. Results : 1.Homnis Placenta Herbal acupuncture inhibited iNOS mRNA and NO in RAW 264.7 cell of LPS-induced rheumatoid arthritis in a dose dependent manner. 2.Homnis Placenta Herbal acupuncture also showed significant inhibition of $TNF-{\alpha}$ & $NF-{\kappa}B$ p65, activation, synovial hyperplasia, angiogenesis and fibrosis in synovial membrane of knee joint of mice. Conclusion : These results suggest that Homnis Placenta Herbal acupuncture has an therapeutic effects on LPS induced-rheumatoid arthritis by inhibiting $TNF-{\alpha}$ activation.