Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine production via NF-κB and MAPK inactivation in RAW 264.7 cells

Park, Hyo-Hyun; Kim, Mi Jin; Li, Ying; Park, Young Na; Lee, Ji‐Ean; Lee, Youn Ju; Kim, Sun-Gun; Park, Hyun‐Je; Son, Jong Keun; Chang, Hyeun Wook; Lee, Eunkyung

doi:10.1016/j.intimp.2012.12.005

Cited by 75 publications

(47 citation statements)

References 34 publications

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“…Britanin was isolated from Inulae Flos by methanol extraction as described previously (Park et al ., 2013). Britanin was dissolved in 0.1% (v/v) dimethyl sulfoxide (DMSO), which did not affect BMMCs viability or activation.…”

Section: Methodsmentioning

confidence: 99%

“…In this previous report, we isolated three major sesquiterpenes by HPLC, and described the inhibitions of degranulation and eicosanoid generation by britanin and tomentosin in SCF-induced BMMCs (Lu et al ., 2012a). In addition, we previously also found that the ethanol extract of I. japonica suppressed macrophages activation by LPS and that britanin suppressed the productions of nitric oxide, PGE 2 and proinflammatory cytokines in LPS-stimulated RAW264.7 cells (Choi et al ., 2010; Park et al ., 2013). However, the mechanisms underlying the inhibitions of degranulation and eicosanoid generation by britanin have not been well established.…”

Section: Introductionmentioning

confidence: 99%

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Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

Park

et al. 2014

Biomolecules & Therapeutics

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The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of PGD2 and LTC4 in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase Cγ1 (PLCγ1)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase and p38), and the nuclear factor-κB (NF-κB) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

Park

et al. 2014

Biomolecules & Therapeutics

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“…9) As a continuing study, we evaluated the compounds isolated from Inulae flos extracts and tomentosin isolated from the ethyl acetate fraction showed anti-inflammatory activities.…”

Section: )mentioning

confidence: 99%

Suppressive Effect of Tomentosin on the Production of Inflammatory Mediators in RAW264.7 Cells

Park

Kim

et al. 2014

Biological & Pharmaceutical Bulletin

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In this study, tomentosin, a sesquiterpene lactone was isolated from Inulae flos and its biological activities were investigated. The effects of tomentosin on the production of inflammatory mediators as well as on nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase activation were evaluated in RAW264.7 cells. Tomentosin decreased the production of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) by suppressing the protein expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, respectively. Additionally, tomentosin reduced the release of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Tomentosin not only attenuated lipopolysaccharide (LPS)-induced NF-κB activation via the abrogation of inhibitory (I)κBα degradation and caused a subsequent decrease in nuclear p65 level, but it also suppressed the phosphorylation of MAP kinases (p38 and c-Jun N terminal kinase (JNK)). These results indicate that tomentosin exerts anti-inflammatory activities through the inhibition of inflammatory mediators (NO, iNOS, PGE 2 , COX-2, TNF-α, and IL-6) by regulating NF-κB activation and phosphorylation of p38/JNK kinases in macrophages, thus suggesting that tomentosin could be a potential agent for the treatment of inflammatory diseases. Key words tomentosin; inflammatory mediator; nuclear factor (NF)-κB; mitogen-activated protein (MAP) kinaseInflammation is the host response to infection and injury, but if it is left uncontrolled, the inflammatory mediators become involved in the pathogenesis of many inflammatory disorders.1) Macrophages play a crucial role in both the specific and non-specific immune responses to microbial and viral infections. When activated by stimuli such as lipopolysaccharide (LPS), macrophages produce a variety of inflammatory mediators such as prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) and pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β) and IL-6.Expression of these inflammatory mediators is regulated by the activation of nuclear factor-kappaB (NF-κB).2) Also, inflammatory mediators including cytokines or mitogenactivated protein (MAP) kinases such as p38 and c-Jun N terminal kinase (JNK) stimulate the pathways by activating the inhibitor κB kinase (IKK).3,4) In unstimulated cells, NF-κB is located in the cytoplasm as an inactive complex bound to its inhibitory protein (IκB). During the process of inflammation, the IKK phosphorylates IκB, inducing its ubiquitination and degradation of IκBα. The free NF-κB then translocates to the nucleus, where it binds to κB-binding sites in the promoter regions of target genes and regulates the expression of various genes, including inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2), and inflammatory cytokines. 5-7)Our previous studies have shown that the ethanol extract of Inulae flos is a potent inhibitor of inflammatory mediators. 8)Recently, it was shown that britanin isolated from Inulae flos inhibited the production of inflammatory medi...

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“…We also isolated several compounds from I. japonica and determined their anti-inflammatory activities [33]. Britanin, another compound isolated from the flowers of I. japonica, inhibited the production of NO and prostaglandin E2 (PGE2) in LPS-stimulated RAW264.7 cells [25]. In this paper, we further isolated 1,6α-dihydroxy-4αH-1,10-secoeudesma-5(10),11(13)-dien-12,8β-olide (SE), 6α-isobutyryloxy-1-hydroxy-4αH-1,10-secoeudesma-5(10),11(13)-dien-12,8β-olide (IBSE), and 6α-isovaleryloxy-1-hydroxy-4αH-1,10-secoeudesma-5(10),11(13)-dien-12,8β-olide (IVSE) from I. japonica, evaluated their antiinflammatory effect by determining the activities on LPS-induced NO production, and investigated the related molecular mechanism.…”

Section: Introductionmentioning

confidence: 99%

IVSE, isolated from Inula japonica,suppresses LPS-induced NO production via NF-κB and MAPK inactivation in RAW264.7 cells

et al. 2015

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Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine production via NF-κB and MAPK inactivation in RAW 264.7 cells

Cited by 75 publications

References 34 publications

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

Suppressive Effect of Tomentosin on the Production of Inflammatory Mediators in RAW264.7 Cells

IVSE, isolated from Inula japonica,suppresses LPS-induced NO production via NF-κB and MAPK inactivation in RAW264.7 cells

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