• 대한의생명과학회지
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• 제18권4호
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• pp.338-344
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• 2012

Mollugin is the active compound of Rubia cordifolia, a well known herb widely used in alternative medicines for the treatment of various inflammatory diseases including arthritis and uteritis. In the present study, we investigated the anti-inflammatory effects of mollugin in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. Treatment with mollugin significantly inhibited LPS-induced release of nitric oxide, prostaglandin $E_2$, and inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6. In addition, mollugin suppressed LPS-induced nuclear factor-kappa B (NF-${\kappa}B$) transcriptional activity. These results suggest that mollugin inhibits LPS-induced expression of inflammatory molecules via NF-${\kappa}B$, at least in part, and indicate the potential value of mollugin as a valuable new drug candidate for the treatment of various inflammatory diseases.

• 대한의생명과학회지
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• 제25권2호
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• pp.196-200
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• 2019

Effect of retinoids, i.e., all-trans retinoic acid and 13-cis retinoic acid, on the activity of nitric oxide synthase (NOS) was evaluated in human malignant keratinocytes to examine the possible correlation of retinoids with NOS activities. All-trans retinoic acid and 13-cis retinoic acid did not alter the nitric oxide (NO) production. However, in the presence of lipopolysaccharide (LPS, $1{\mu}g/mL$), they significantly increased NO release in a dose-dependent manner until 48 h at concentrations of $50{\sim}100{\mu}M$. The degree of upregulation of NO by all-trans retinoic acid and 13-cis retinoic acid increased up to 35% and 37%, respectively, compared to that by the control, which demonstrated the upregulation of LPS-inducible nitric oxide synthase (iNOS)-dependent generation of NO as well as showing a crucial link between retinoids-induced activity and NOS. Findings of this study now suggest that the upregulation of LPS-iNOS activity may be associated with modulation of retinoids-induced control of cellular developmental processes, which may produce new therapeutics of retinoids in the complexity of how NO affects human keratinocytes.

• Journal of Applied Biological Chemistry
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• 제65권1호
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• pp.23-31
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• 2022

Oxidative stress and neuroinflammation play important roles in the pathogenesis of Alzheimer's disease (AD). This study investigated the protective effects of paeoniflorin (PF) against neuronal oxidative stress and neuroinflammation in lipopolysaccharide (LPS)-induced mice. The brains of LPS-injected control group showed significantly increased neuroinflammation by activating the nuclear factor kappa B (NF-κB) pathway and increasing inflammatory mediators. However, administration of PF significantly attenuated oxidative stress by inhibiting lipid peroxidation, nitric oxide levels, and reactive oxygen species production in the brain; PF at doses of 5 and 10 mg/kg/day downregulated the expression of NF-κB pathway-related proteins and significantly decreased inflammatory mediators including inducible nitric oxide synthase and cyclooxygenase-2. Moreover, the levels of brain-derived neurotrophic factor and its receptor, tropomycin receptor kinase B, were significantly increased in PF-treated mice. Furthermore, acetylcholinesterase activity and the ration of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X were significantly reduced by PF in the brains of LPS-induced mice, resulting in the inhibition of cholinergic dysfunction and neuronal apoptosis. Thus, we can conclude that administration of PF to mice prevents the development of LPS-induced AD pathology through the inhibition of neuronal oxidative stress and neuroinflammation, suggesting that PF has a therapeutic potential for AD.

• Journal of Trauma and Injury
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• 제21권2호
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• pp.120-127
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• 2008

Purpose: Many studies on the time course of inducible nitric oxide synthase (iNOS) gene expression have been performed in the LPS (Lipopolysaccharide)-induced endotoxemic model, but there have been few experimental approaches to continuous peritonitis-induced sepsis model. We conducted this study to establish basic data for future sepsis-related research by investigating the time course of iNOS gene expression and the relationship with the production of inflammatory mediators in the early sepsis model induced by cecal ligation and puncture (CLP). Methods: Male Sprague-Dawley rats were operated on by sing the CLP method to induce of peritonitis; and then, they were sacrificed and samples of blood and lung tissues were obtained at various times (1,2,3,6,9 and 12 h after CLP). We observed the expression of iNOS mRNA from lung tissues and measured the synthesis of nitric oxide, $IL-1{\beta}$, and $TNF-{\alpha}$ from the blood. Results: iNOS mRNA began to be expressed at 3 h and was maintained untill 12 h after CLP. The nitric oxide concentration was increased significantly at 6 h, reached its peak level at 9 h, and maintained a plateau untill 12 h after CLP. $TNF-{\alpha}$ began to be detected at 3 h, increased gradually, and decreased steeply from 9 h after CLP. $IL-1{\beta}$ showed its peak level at 6 h after CLP, and tended to decrease without significance. Conclusion: We observed that the iNOS gene was expressed later in peritonitis-induced sepsis than in LPS-induced sepsis. Nitric oxide and key inflammatory mediators were also expressed later in peritonitis-induced sepsis than in LPS-induced sepsis.

• Korean Journal of Acupuncture
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• 제28권1호
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• pp.61-69
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• 2011

Objectives : The purpose of this study is to investigate effects of White Ginseng-Ejung-tang acupuncture solution (EJ) on nitric oxide (NO) and of hydrogen peroxide production in RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS). Methods : Cell viability was measured by modified MTT assay. NO production was measured by Griess reagent assay. Hydrogen peroxide production was measured by dihydrorhodamine 123 (DHR) assay. Significant differences were examined by using a Student's t-test. Results : The results of the experiment are as follows. 1. EJ did not show cell toxicity against RAW 264.7 cells for 24 hr incubation at the concentrations of up to $200\;{\mu}g$/mL in RAW 264.7 cells. 2. EJ significantly inhibited NO production for 24 hr incubation in RAW 264.7 cells (p <0.05). 3. EJ significantly inhibited the LPS-induced production of NO for 24 hr incubation in RAW 264.7 cells (p <0.05). 4. EJ significantly inhibited the LPS-induced production of hydrogen peroxide for 16, 24, 40, 48, 64, and 72 hr incubation in RAW 264.7 cells (p <0.05). Conclusions : These results suggest that EJ has an anti-inflammtory property related with its inhibition of NO and hydrogen peroxide production in LPS-induced macrophages.

• Fisheries and Aquatic Sciences
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• 제17권1호
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• pp.27-35
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• 2014

Marine brown algae have been identified as a rich source of structurally diverse bioactive compounds. Whether Myagropsis yendoi ethanolic extracts (MYE) inhibit inflammatory responses was investigated using lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. MYE inhibited LPS-induced nitric oxide (NO) production in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase in BV-2 cells. MYE also reduced the production of pro-inflammatory cytokines in LPS-stimulated BV-2 cells. LPS-induced nuclear factor-${\kappa}B$ (NF-${\kappa}B$) transcriptional activity and NF-${\kappa}B$ translocation into the nucleus were significantly inhibited by MYE treatment through preventing degradation of the inhibitor ${\kappa}B-{\alpha}$. Moreover, MYE inhibited the phosphorylation of AKT, ERK, JNK, and p38 mitogen-activated protein kinase in LPS-stimulated BV-2 cells. These results indicate that MYE is a potential source of therapeutic or functional agents for neuroinflammatory diseases.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• Preventive Nutrition and Food Science
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• 제15권2호
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• pp.92-97
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• 2010

Luteolin and chicoric acid are the most abundant phytochemicals in dandelion (Taraxacum officinale) leaf. In this study, four kinds of extraction methods [hot water, ambient temperature (AT) water, ethanol, and methanol] were applied to analyze the contents of both phytochemicals and verify their anti-inflammatory and antioxidative activities. The methanol extract showed the most potent nitric oxide (NO) inhibitory effect. The luteolin and chicoric acid concentrations were 3.42 and $12.86\;{\mu}g/g$ dandelion leaf in the methanol extract. The NO-suppressive effect of luteolin and chicoric acid was identified in a dose-dependent manner with $IC_{50}$ values of $21.2\;{\mu}M$ and $283.6\;{\mu}M$, respectively, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells without cytotoxicity. Malondialdehyde (MDA) concentration, as an index for free radical injury on cell membrane, was also dose-dependently inhibited by the two compounds. The suppressive effect was further examined using mRNA and protein expression levels, which were attributable to the inhibition of inducible nitric oxide synthase (iNOS). These results suggest that two phytochemicals in dandelion leaf, luteolin and chicoric acid, may play an important role in the amelioration of LPS-induced oxidative stress and inflammation.

• 생약학회지
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• 제35권4호통권139호
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• pp.283-287
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• 2004

The effect of water extract from Cnidii Rhizoma (CRW) on proliferation of human breast cancer cells, nitric oxide production, nitric oxide synthase expression, and ornithine decarboxylase activity was tested. CRW inhibited the growth of both estrogen-dependent MCF-7 and estrogen-independent MDA-MB-23I human breast cancer cells. Lipopolysaccharide-induced nitric oxide (NO) production was significantly reduced by CRW at the concentration of 0.5, 1.0 and 5.0 mg/ml. Expression of inducible nitric oxide synthase (iNOS) was also suppressed with the treatment of CRW in Raw 264.7 cells. CRW inhibited induction of ornithine decarboxylase by 12-0-tetradecanoylphorbol-13-acetate, a key enzyme of polyamine biosynthesis, which is enhanced in tumour promotion. Therefore, CRW is worth further investigation with respect to breast cancer chemoprevention or therapy.

• 한국균학회지
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• 제45권4호
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• pp.336-344
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• 2017

본 연구에서는 우리나라 주요 산과 섬에서 분리한 비병원성 야생효모들 중 항염 효과가 우수했던 Meyerozyma guilliermondii YJ34-2와 Rhodotorula graminis YJ36-1의 무세포 추출물들을 제조하여 대식세포 계열 RAW 264.7 세포에 대한 이들의 NO 생성 저해활성과 세포독성을 조사하였다. NO 생성 저해활성은 농도 의존적으로 높아 M. guilliermondii YJ34-2와 R. graminis YJ36-1 무세포 추출물을 1,000 mg/mL 처리 시 각각 51.6%와 81.4%를 보여 가장 높았고 RAW 264.7 세포에 대한 세포 생존율도 1,000 mg/mL 처리시 각각 88.4% (${\pm}3.1$)와 77.1% (${\pm}0.3$)로 가장 높았다. 두 효모들의 무세포 추출물 처리에 따른 prostaglandin $E_2$ 생성량은 농도 의존적으로 감소하여 각각의 무세포 추출물을 1,000 mg/mL 처리했을 때, tumor necrosis factor $(TNF)-{\alpha}$ 생성량이 59.2 (${\pm}43.1$), 73.2 (${\pm}38.1$)%로 감소하였고 prostaglandin $E_2$의 생성량도 52.8 (${\pm}1.9$), 71.2 (${\pm}3.7$)%로 감소하여 이 두 효모들의 항균활성을 검증할 수 있었다. 두 효모들의 NO 생성 저해물질 최적 생산조건을 조사한 결과 M. guilliermondii YJ34-2를 yeast extract-peptone- dextrose (YPD) 배지에 접종하여 $30^{\circ}C$에서 24시간 배양하여 얻은 무세포 추출물이 가장 높은 51.6 (${\pm}0.3$)%의 NO 생성 저해율을 보였고 R. graminis YJ36-1를 YPD 배지에 접종하여 $25^{\circ}C$에서 24시간 배양하였을 때 81.4 (${\pm}1.3$)%의 가장 높은 NO 생성 저해활성을 보였다.