• Preventive Nutrition and Food Science
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• 제22권1호
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• pp.50-55
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• 2017

Raphanus sativus L. (RS) is a cruciferous vegetable that is widely consumed in Korea. The anticancer activity of leaves of RS (RSL) extract has been investigated; however, no studies focused on its anti-inflammatory effects. Therefore, the aim of the current study was to evaluate the anti-inflammatory effects of RSL extract. In brief, RSL powder was fractionated into n-hexane, chloroform, ethyl acetate, n-butanol, and water-soluble fractions. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with each fraction for initial screening. It was found that the chloroform fraction significantly inhibited nitric oxide release in LPS-stimulated RAW264.7 cells with a half maximal inhibitory concentration value of $196{\mu}g/mL$. In addition, the mRNA and protein expression levels of inducible nitric oxide synthase, measured using reverse transcriptase-polymerase chain reaction and western blotting, respectively, were reduced in a concentration-dependent manner. Moreover, the inflammatory cyclooxygenase-2 enzyme expression decreased. Furthermore, the expression of nuclear factor-kappa B ($NF-{\kappa}B$), the key regulator of the transcriptional activation of the inflammatory cytokine genes, was reduced by the RSL chloroform fraction. Therefore, the results of our study suggest that RSL exhibits anti-inflammatory effects in LPS-stimulated macrophages via $NF-{\kappa}B$ inactivation.

• 한국식품영양학회지
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• 제32권5호
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• pp.565-570
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• 2019

Proteasome inhibitors can improve the efficiency of cancer treatments by inhibiting nuclear factor ${\kappa}B$($NF-{\kappa}B$) activation in cancer cells. Lentils are a type of beans of which consumption of such beans is increasing. The purpose of this study was to investigate the effects of lentils extract (LE) on the proteasomal activities, $NF-{\kappa}B$ activation, and cell cycle in HepG2 human liver cancer cells. LE treatments inhibited proteasomal activities at concentrations of 10, 50, and $100{\mu}g/mL$ respectively, and repressed $NF-{\kappa}B$ activation at concentrations of 1, 10, and $100{\mu}g/mL$ respectively, in HepG2 cells. LE treatments at concentrations of 1, 10, and $100{\mu}g/mL$ respectively, increased sub-G1 cell population in HepG2 cells, which may be the result of apoptosis. The results suggest that LE inhibited $NF-{\kappa}B$ activation partially with its proteasome inhibitory activities, and the increase of sub-G1 cell population was induced partially, by inhibition of $NF-{\kappa}B$ activation in HepG2 cells.

• Natural Product Sciences
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• 제17권3호
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• pp.250-255
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• 2011

The immune system is finely balanced by the activities of pro-inflammatory and anti-inflammatory mediators or cytokines. Unregulated activities of these mediators can lead to the development of various inflammatory diseases. A variety of safe and effective anti-inflammatory agents are available with many more drugs under development. Of the natural compounds, the sesquiterpenes (nootkatone, ${\alpha}$-cyperone, valencene and ${\alpha}$-selinene) isolated from C. rotundus L. have received much attention because of their potential antiinflammatory effects. However, limited studies have been reported regarding the influence of sesquiterpene structure on anti-inflammatory activity. In the present study, the anti-inflammatory potential of four structurally divergent sesquiterpenes was evaluated in lipopolysaccaride (LPS)-stimulated RAW 264.7 cells, murine macrophages. Among the four sesquiterpenes, ${\alpha}$-cyperone and nootkatone, showed stronger anti-inflammatory and a potent NF-${\kappa}B$ inhibitory effect on LPS-stimulated RAW 264.7 cells. Molecular analysis revealed that various inflammatory enzymes (iNOS and COX-2) were reduced significantly and this correlated with downregulation of the NF-${\kappa}B$ signaling pathway. Additionally, electrophoretic mobility shift assays (EMSA) elucidated that nootkatone and ${\alpha}$-cyperone dramatically suppressed LPS-induced NF-${\kappa}B$-DNA binding activity using 32Plabeled NF-${\kappa}B$ probe. Hence, our data suggest that ${\alpha}$-cyperone and nootkatone are potential therapeutic agents for inflammatory diseases.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.139-157
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• 2006

In the present study, I have investigated the bee venom (BV) and melittin (a major component of BV) -mediated anti-proliferative effects, and defined its mechanisms of action in cultured rat aortic vascular smooth muscle cells (VSMCs). BV and melittin $(0.4{\sim}0.8\;{\mu}g/ml)$ effectively inhibited 50 ng/ml platelet derived growth factor BB (PDGF-BB)-induced VSMCs proliferations. The regulation of apoptosis has attracted much attention as a possible means of eliminating excessively proliferating VSMCs. In the present study, the treatment of BV and melittin strongly induced apoptosis of VSMCs. I examined the effects on $NF-{\kappa}B$ activation to investigate a possible mechanism for anti-proliferative effects of BV and melittin, the PDGF-BB-induced $I{\kappa}B{\alpha}$ phosphorylation and its degradation were potently inhibited by melittin, and DNA binding activity and nuclear translocation of $NF-{\kappa}B$ p50 subunit in response to the action of PDGF-BB were potently attenuated by melittin. In further investigations, melittin markedly inhibited the PDGF-BB-induced phosphorylation of Akt but not ERK1/2, upstream signals of $NF-{\kappa}B$. Treatment of melittin also potently induced pro-apoptotic protein p53, Bax, and caspase-3 expression, but decreased anti-apoptotic protein Bcl-2 expression. These results suggest that the anti-proliferative effects of BV and melittin in VSMCs through induction of apoptosis via suppressions of $NF-{\kappa}B$ and Akt activation, and enhancement of apoptotic signal pathway. Based on these results, BV acupuncture can be a candidate as a therapeutic method for restenosis and atherosclerosis.

• Archives of Pharmacal Research
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• 제29권7호
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• pp.591-597
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• 2006

Aerial parts of Artemisia asiatica (Compositae) have been traditionally used as an oriental medicine for the treatment of inflammatory and ulcerogenic diseases. In the present study, artemisolide was isolated as a nuclear factor $(NF)-{\kappa}B$ inhibitor from A. asiatica by activity-guided fractionation. Artemisolide inhibited $NF-{\kappa}B$ transcriptional activity in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an $IC_{50}$ value of $5.8\;{\mu}M$. The compound was also effective in blocking $NF-{\kappa}B$ transcriptional activities elicited by the expression vector encoding the $NF-{\kappa}B$ p65 or p50 subunits bypassing the inhibitory kB degradation signaling $NF-{\kappa}B$ activation. The macrophages markedly increased their $PGE_2$ and NO production upon exposure to LPS alone. Artemisolide inhibited LPS-induced $PGE_2$ and NO production with $IC_{50}$ values of $8.7\;{\mu}M$ and $6.4\;{\mu}M$, respectively, but also suppressed LPS-induced synthesis of cyclooxygenase (COX)-2 or inducible NO synthase (iNOS). Taken together, artemisolide is a $NF-{\kappa}B$ inhibitor that attenuates LPS-induced production of $PGE_2$ or NO via down-regulation of COX-2 or iNOS expression in macrophages RAW 264.7. Therefore, artemisolide could represent and provide the anti-inflammatory principle associated with the traditional medicine, A. asiatica.

• Food Science and Biotechnology
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• 제16권5호
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• pp.728-733
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• 2007

Bamboo grass, Sasa quelpaertensis, is a native plant to Jeju Island, Korea. The leaves of Sasa plants are widely used in traditional Korean medicine to treat inflammation-related diseases. We investigated the effect of hot water extract from Sasa quelpaertensis leaves (HWE-SQ) on nitric oxide (NO) production and nuclear $factor-{\kappa}B\;(NF-{\kappa}B)$ activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. HWE-SQ inhibited LPS-induced NO production and inducible NO synthase (iNOS) protein expression in a dose-dependent manner. Reporter gene assays indicated that HWE-SQ decreases LPS-induced $NF-{\kappa}B$ transcriptional activation. However, HWE-SQ did not affect the phosphorylation and degradation of inhibitory ${\kappa}B{\alpha}\;(1{\kappa}B{\alpha})$. HWE-SQ also directly inhibited iNOS enzyme activity in a dose-dependent manner. These results suggest that HWE-SQ suppresses NO synthesis in macrophages by attenuating $NF-{\kappa}B-mediated$ iNOS protein expression and inhibiting iNOS enzymatic activity, thereby implicating a mechanism by which HWE-SQ is able to ameliorate inflammation-related diseases by limiting excessive or prolonged NO production in pathological events.

• 한방안이비인후피부과학회지
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• 제32권3호
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• pp.48-57
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• 2019

Objectives : This study examined the inhibitory effects of Wisaengtang(WST) on inflammatory mediators($NF-{\kappa}B$, COX-2, iNOS, IL-6) in cellular inflammatory responses induced by lipopolysaccharide(LPS). Methods : To investigate the cytotoxicity of WST, MTT assay was used. The inhibitory effects of inflammatory mediators were confirmed by real-time PCR and DPPH scavenging activity was measured to confirm the antioxidative effect. Results : When the $NF-{\kappa}B$ mRNA expression was inhibited, the levels of COX-2, iNOS, and IL-6 mRNA in the inflammatory response decreased significantly. iNOS is involved in the production of nitric oxide (NO), and it is confirmed that WST inhibits the expression of iNOS mRNA and thus the production of NO. Conclusions : These results suggest that WST can be a therapeutic substance for oxidation and inflammation through elimination of DPPH free radical and inhibition of $NF-{\kappa}B$ activity.

• 한국식품영양과학회지
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• 제45권2호
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• pp.194-201
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• 2016

본 연구에서는 lipopolysaccharide(LPS)로 자극한 마우스 대식세포인 RAW 264.7 세포에서 가락진두발 에탄올 추출물(CNYEE)의 항염증 효과를 알아보기 위하여 nitric oxide(NO)와 pro-inflammatory cytokine의 분비량을 확인하였다. 그 결과 CNYEE 모든 농도에서 LPS만을 처리한 대조군과 비교하였을 때 유의성 있게 NO와 pro-inflammatory cytokine의 분비량을 저해하였으며, 특히 $100{\mu}g/mL$ 농도에서는 IL-6의 분비량을 70% 이상 억제하였고, TNF-${\alpha}$ 및 IL-$1{\beta}$의 분비량은 50% 이상의 억제 효과를 나타내었다. CNYEE에 의한 염증매개물질의 분비 감소가 전사인자인 nuclear factor-${\kappa}B$(NF-${\kappa}B$)의 핵 내 전이 pathway를 저해함으로써 나타난 결과인지 확인하기 위하여 iNOS, COX-2 및 NF-${\kappa}B$ p65의 단백질 발현량을 관찰한 결과, 비교적 낮은 농도인 $50{\mu}g/mL$에서 40% 이상의 저해능을 보인 것으로 보아 NO와 cytokine의 분비 억제 결과가 NF-${\kappa}B$ pathway를 저해함으로써 나타난 것임을 유추할 수 있었다. 또한 LPS에 의해 증가한 mitogen-activated protein kinases의 인산화를 확인한 결과, CNYEE 처리에 의해 농도 의존적으로 유의성 있게 저해되었다. 이러한 결과를 종합해볼 때 가락진두발 에탄올 추출물은 염증매개물질의 분비를 효과적으로 저해함으로써 추후 천연물로서 염증 치료제의 개발이 가능할 것으로 생각한다.

• Bulletin of the Korean Chemical Society
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• 제35권8호
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• pp.2361-2366
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• 2014

A new aliphatic acid amide, ZP-amide F (1), and eight known compounds, including bungeanumamide A (2), tumuramide C (3), ZP-amide A (4), ZP-amide B (5), ZP-amide D (6), hyperin (7), quercitrin (8), and (-)-sesamin (9), were isolated from pericarps of Zanthoxylum piperitum. The effects of these compounds on $TNF{\alpha}$-induced NF-${\kappa}B$ activation and transactivational activity of PPARs, including $PPAR{\alpha}$, $PPAR{\beta}({\delta})$ and $PPAR{\gamma}$ subtypes, were evaluated. Compounds 7 and 9 exhibited potent inhibitory effects on $TNF{\alpha}$-induced NF-${\kappa}B$ activation with $IC_{50}$ values of 5.50 and $8.10{\mu}M$, respectively. Aliphatic acid amide compounds 3, 4 and 6 displayed enhanced effects on PPAR transactivational activity with $EC_{50}$ values of 47.12, 19.13 and $12.02{\mu}M$, respectively. Among them, compound 4 demonstrated an increase in $PPAR{\alpha}$ transactivational activity, compound 3 showed a moderate increase on all PPAR subtypes, whereas compound 6 displayed weak PPAR transactivational activity.

• 대한한의학회지
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• 제29권5호
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• pp.111-117
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• 2008

Objectives and methods : Previous mechanistic studies suggest the cyclooxygenase-2 (COX-2) inhibitors represent the good candidates against tumor progression. MeOH extract of the stem barks of Euonymus alatus induced the strong inhibition of COX-2. A phenolic compound responsible for the anti- COX-2 known to involve in tumor adhesion and invasion has been studied through the methanol extracts. The compound, rosmarinic acid (ROS-A) was an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. ROS-A showed a strong inhibitory effect of COX-2 activity in a concentration-dependent manner. Then we have measured the IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production related the immune regulation, induction of inflammatory related genes. Results and Conclusions :Hep3B cells produce proinflammatory cytokines of IL-1${\beta}$, IL-6 and TNF-${\alpha}$ while ROS A inhibited the cytokines production. Since IL-1${\beta}$, IL-6 and TNF-${\alpha}$ need the transcription factors such as nuclear factor- ${\kappa}$B (NF-${\kappa}$B) and activated protein-1 (AP-1), we measured the transcription factors. ROS-A inhibited the activation of p65, p50, c-Rel subunits of NF-${\kappa}$B and AP-1 transcription factors. These findings indicate that ROS A from the stem bark of E. alatus inhibits proliferation in metastatic cancer cells. It was suggested that stem barks of E. alatus could be suitable for anti-cancer drugs.