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Berteroin present in cruciferous vegetables exerts potent anti-inflammatory properties in murine macrophages and mouse skin.

Jung YJ, Jung JI, Cho HJ, Choi MS, Sung MK, Yu R, Kang YH, Park JH - Int J Mol Sci (2014)

Bottom Line: Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages.Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor β activated kinase-1.Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. betyloving@naver.com.

ABSTRACT
Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of κBα (IκBα) and nuclear factor-κB p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor β activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent.

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Proposed mechanisms underlying the anti-inflammatory effects of berteroin. Berteroin inhibits IL-1 receptor-associated kinase (IRAK1) degradation, which results in decreased phosphorylation of transforming growth factor β activated kinase-1 (TAK1) leading to the reduction of IκB kinase (IKK), p38 mitogen activated protein kinase (MAPK), and extracellular regulated kinase (ERK)1/2 phosphorylation and subsequent reduction of IκB phosphorylation and degradation. Decreased AKT phosphorylation also contributes to the reduction of IKK activation. The resulting high levels of IκB prevents p65 translocation from the cytosol to the nucleus thereby preventing transcription of inducible metric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 leading to a decreased inflammatory response.
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ijms-15-20686-f007: Proposed mechanisms underlying the anti-inflammatory effects of berteroin. Berteroin inhibits IL-1 receptor-associated kinase (IRAK1) degradation, which results in decreased phosphorylation of transforming growth factor β activated kinase-1 (TAK1) leading to the reduction of IκB kinase (IKK), p38 mitogen activated protein kinase (MAPK), and extracellular regulated kinase (ERK)1/2 phosphorylation and subsequent reduction of IκB phosphorylation and degradation. Decreased AKT phosphorylation also contributes to the reduction of IKK activation. The resulting high levels of IκB prevents p65 translocation from the cytosol to the nucleus thereby preventing transcription of inducible metric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 leading to a decreased inflammatory response.

Mentions: We demonstrated that berteroin effectively inhibited LPS-stimulated inflammatory responses in murine macrophages as well as TPA-stimulated skin edema formation in mice. Berteroin prevented LPS-induced phosphorylation of TAK1, AKT, p38 MAPK, and ERK1/2, IKKα/β, and IκBα as well as the degradation of IRAK1 and IκBα in murine macrophages. The increased IκBα bound to NF-κB and thereby prevented the translocation of this transcription factor to the nucleus. As a result, berteroin inhibited expression of iNOS, COX-2, IL-1β, IL-6, and TNF-β (Figure 7). The finding that only 500 nmoles of berteroin effectively inhibited skin inflammation in mice suggests that berteroin is a good candidate as an anti-inflammatory agent.


Berteroin present in cruciferous vegetables exerts potent anti-inflammatory properties in murine macrophages and mouse skin.

Jung YJ, Jung JI, Cho HJ, Choi MS, Sung MK, Yu R, Kang YH, Park JH - Int J Mol Sci (2014)

Proposed mechanisms underlying the anti-inflammatory effects of berteroin. Berteroin inhibits IL-1 receptor-associated kinase (IRAK1) degradation, which results in decreased phosphorylation of transforming growth factor β activated kinase-1 (TAK1) leading to the reduction of IκB kinase (IKK), p38 mitogen activated protein kinase (MAPK), and extracellular regulated kinase (ERK)1/2 phosphorylation and subsequent reduction of IκB phosphorylation and degradation. Decreased AKT phosphorylation also contributes to the reduction of IKK activation. The resulting high levels of IκB prevents p65 translocation from the cytosol to the nucleus thereby preventing transcription of inducible metric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 leading to a decreased inflammatory response.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264190&req=5

ijms-15-20686-f007: Proposed mechanisms underlying the anti-inflammatory effects of berteroin. Berteroin inhibits IL-1 receptor-associated kinase (IRAK1) degradation, which results in decreased phosphorylation of transforming growth factor β activated kinase-1 (TAK1) leading to the reduction of IκB kinase (IKK), p38 mitogen activated protein kinase (MAPK), and extracellular regulated kinase (ERK)1/2 phosphorylation and subsequent reduction of IκB phosphorylation and degradation. Decreased AKT phosphorylation also contributes to the reduction of IKK activation. The resulting high levels of IκB prevents p65 translocation from the cytosol to the nucleus thereby preventing transcription of inducible metric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 leading to a decreased inflammatory response.
Mentions: We demonstrated that berteroin effectively inhibited LPS-stimulated inflammatory responses in murine macrophages as well as TPA-stimulated skin edema formation in mice. Berteroin prevented LPS-induced phosphorylation of TAK1, AKT, p38 MAPK, and ERK1/2, IKKα/β, and IκBα as well as the degradation of IRAK1 and IκBα in murine macrophages. The increased IκBα bound to NF-κB and thereby prevented the translocation of this transcription factor to the nucleus. As a result, berteroin inhibited expression of iNOS, COX-2, IL-1β, IL-6, and TNF-β (Figure 7). The finding that only 500 nmoles of berteroin effectively inhibited skin inflammation in mice suggests that berteroin is a good candidate as an anti-inflammatory agent.

Bottom Line: Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages.Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor β activated kinase-1.Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. betyloving@naver.com.

ABSTRACT
Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of κBα (IκBα) and nuclear factor-κB p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor β activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent.

Show MeSH
Related in: MedlinePlus