[6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-κB in phorbol ester-stimulated mouse skin

Kim, Sue Ok; Kundu, Joydeb Kumar; Shin, Young Kee; Park, Jin‐Hong; Cho, Myung‐Haing; Kim, Taeyoon; Surh, Young‐Joon

doi:10.1038/sj.onc.1208446

Cited by 283 publications

(201 citation statements)

References 55 publications

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“…The hyperplasia in DMBA-treated skin was associated with increasingly higher levels of COX-2 expression, an enzyme associated with inflammation and tumorigenesis (26). As shown in Fig.…”

Section: Analysis Of Mutations In Codon 61 Of Ha-ras Oncogene In Skinmentioning

confidence: 73%

Synergistic Effects of Combined Phytochemicals and Skin Cancer Prevention in SENCAR Mice

Kowalczyk

Tolstykh

et al. 2010

Cancer Prevention Research

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The purpose of our study was to determine the inhibitory effect of combined phytochemicals on chemically induced murine skin tumorigenesis. Our hypothesis was that concurrent topical and dietary treatment with selected compounds would lead to more efficient prevention of skin cancer. We tested ellagic acid and calcium D-glucarate as components of diets, while resveratrol was applied topically; grape seed extract was applied topically or in the diet. The 4-week inflammatory-hyperplasia assay based on the 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis model in SENCAR mice was used. We have found that all the selected combinations caused a marked decrease of epidermal thickness compared with the DMBA-treated group and also with groups treated with a single compound and DMBA. All combinations of resveratrol with other compounds showed a synergistic effect on hyperplasia and Ha-ras mutations. Skin tissue of mice receiving the combinations showed decreased cell proliferation and Bcl2 expression; decreased p21, a regulator of cell cycle; and decreased marker of inflammation cyclooxygenase-2. All the selected combinations diminished the DMBA-induced mRNA expression of the CYP1B1 level, and also caused a marked decrease of proto-oncogenes c-jun and c-fos, components of transcription factor activator protein. In conclusion, all combinations showed either additive or synergistic effects and their joint actions allowed for decreasing the doses of the compounds. Especially, resveratrol combinations with ellagic acid, grape seed extract, and other phytochemicals are very potent inhibitors of skin tumorgenesis, based on the suppression of epidermal hyperplasia as well as on the modulation of intermediate biomarkers of cell proliferation, cell survival, inflammation, oncogene mutation, and apoptosis.Cancer Prev Res; 3(2); 170-8. ©2010 AACR.

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“…The hyperplasia in DMBA-treated skin was associated with increasingly higher levels of COX-2 expression, an enzyme associated with inflammation and tumorigenesis (26). As shown in Fig.…”

Section: Analysis Of Mutations In Codon 61 Of Ha-ras Oncogene In Skinmentioning

confidence: 73%

Synergistic Effects of Combined Phytochemicals and Skin Cancer Prevention in SENCAR Mice

Kowalczyk

Tolstykh

et al. 2010

Cancer Prevention Research

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“…2 indicated that Ucn1-regulated ICAM1 expression was dependent on COX2. Moreover, Kim et al (2005) found that the induction of COX2 in mouse skin is regulated, at least in part, by an eukaryotic transcription factor NF-kB. Therefore, we examined the effects of PDTC on COX2 expression.…”

Section: Pka-creb Participated In the Signaling Events Leading To Indmentioning

confidence: 99%

Urocortin increased endothelial ICAM1 by cPLA2-dependent NF-κB and PKA pathways in HUVECs

Wan¹,

Liu²,

Li³

et al. 2014

Journal of Molecular Endocrinology

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Urocortin (Ucn1), a member of the corticotrophin-releasing hormone (CRH) family, has been reported to participate in inflammation. The increased expression of intercellular adhesion molecule 1 (ICAM1) plays important roles in inflammation and immune responses. Our previous results demonstrated that Ucn1 significantly enhanced the expression of ICAM1. However, the underlying mechanisms are still unknown. The purpose of this study is to investigate the detailed mechanisms of Ucn1-induced upregulation of ICAM1. Here, we characterized the mechanisms of Ucn1 usage to regulate ICAM1 expression in human umbilical vein endothelial cells (HUVECs). Our data revealed that Ucn1 increased ICAM1 and cyclooxygenase 2 (COX2) expressions in a time-dependent manner via CRH receptor 2 (CRHR2). In addition, COX2 was involved in ICAM1 upregulation. Furthermore, Ucn1 could increase the expression and phosphorylation of cytosolic phospholipases A2 (cPLA2) in a time-dependent manner via CRHR2 and CRHR1. Moreover, ablation of cPLA2 by the inhibitor pyrrophenone or siRNA attenuated the ICAM1 increase induced by Ucn1. In addition, nuclear factor kB (NF-kB) was activated, indicated by the increase in nuclear p65NF-kB expression and phosphorylation of p65NF-kB, depending on cPLA2 and CRHR2 activation. Pyrrolidinedithiocarbamic acid, an inhibitor of NF-kB, abolished the elevation of ICAM1 but not COX2. Also, Ucn1 increased the production of prostaglandin E 2 (PGE 2 ) which further activated protein kinase A (PKA)-CREB pathways dependent of cPLA2 via CRHR2. Moreover, the increase in NF-kB phosphorylation was not affected by the selective COX2 inhibitor NS-398 or the PKA inhibitor H89. In conclusion, these data indicate that Ucn1 increase the ICAM1 expression via cPLA2-NF-kB and cPLA2-COX2-PGE 2 -PKA-CREB pathways by means of CRHR2.

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“…Tais estudos incluem o papel dos compostos na atividade motora, efeito antipirético, analgésico (SUEKAWA et al, 1984), antioxidante (MASUDA et al, 2004), inibidor da angiogênese (KIM et al, 2005), inibidor de metástase de câncer de mama (LEE et al, 2008), antibacteriano (PARK;LEE, 2008), além das atividades imunomoduladoras e anti-inflamatórias que serão tratadas no presente trabalho. Há também estudos abordando suas propriedades físicas (DING et al, 1991) Dentre os componentes, destacam-se o 6-gingerol e o 6-shogaol e gingerdiones, que representam 3% do óleo volátil, sendo os mais abundantes componentes da raiz (ZICK et al, 2008;VRIENS et al, 2008), motivo pelo qual são atualmente as moléculas mais exploradas individualmente (SAHA et al, 2014;KUMAR et al, 2014;DUGASANI, 2010;GAUS et al, 2009;TRIPATHI et al, 2007;ALI el al., 2007;KOH et al, 2009).…”

Section: Gengibre E Seus Componentesunclassified

“…Porém os autores demonstraram que estes mecanismo parece estar relacionado com a interação com a via das MAP quinases com NFkB, em que a MAP quinase p38 ao ser inibida pelo 6-gingerol levava a não fosforilação do IkB-α e da subunidade p65. Culminando assim com a diminuição dos níveis de COX-2 (KIM et al, 2005). Kim et al (2005) demonstraram que o 6-gingerol reduziu os níveis de COX-2, inibiu a translocação da subunidade p65 para o núcleo, e também a inibição da fosforilação do complexo IkB-α em modelos de exposição de cultura de queratinócitos humanos e camundongos hairless à radiação UVB (KIM et al, 2007).…”

Section: Efeito Anti-inflamatório Do Gengibre: Possível Via De Sinaliunclassified

Efeito anti-inflamatório do gengibre e possível via de sinalização

Vieira

Tomiotto

Melo

et al. 2014

Semin. Cienc. Biol. Saude

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O gengibre (Zingiber officinale Roscoe) vem sendo utilizado tanto na medicina natural tradicional quanto contemporânea, sendo descritos mais de 115 componentes do gengibre fresco e seco. Dentre esses componentes, os compostos fenólicos, gingerol e o shoagol, têm sido amplamente estudados apresentando diferentes propriedades destas moléculas como efeito antipirético, analgésico, inibidor da angiogênese, atividades imunomoduladoras, entre outras. Esta revisão tem como objetivo apresentar os componentes do gengibre assim como o seu efeito antagônico sobre o lipopolissacarídeo (LPS), propriedade anti-inflamatória e possível via de sinalização envolvida. O efeito do gengibre sobre o LPS consiste na inibição da produção de Interleucina 12 (IL -12), resultando em menor ativação de macrófagos induzidos pelo LPS; diminuição na expressão de moléculas co-estimulatórias e expressão de MHC classe II e diminuição de Interleucina 2 (IL-2), suprimindo a ativação e proliferação de células T CD4+. A propriedade anti-inflamatória do composto está relacionada com a capacidade de modular o linfócito T, de forma a inibir a eosinofilia, reduzir a quantidade de mastócitos, inibir a liberação de IL-4 e reduzir a resposta Th2. Além disso, pode ocorrer inibição da translocação da subunidade p65 para o núcleo e inibição da fosforilação do complexo IkB-α, culminando com a diminuição dos níveis de COX-2. Através deste estudo, podemos concluir que componentes do gengibre podem atuar antagonicamente sobre o efeito de ativação do LPS em macrófagos, conduzindo um efeito imunomodulador e anti-inflamatório, no qual a possível via de sinalização afetada seja do NFkB com envolvimento das MAPquinases. Palavras-Chave: Zingiber officinale Roscoe. Gingerol. Shogaol. Inflamação AbstractGinger (Zingiber officinale Roscoe) has been used in both traditional and contemporary natural medicine, with over 115 described components of fresh and dried ginger. Among these components, the phenolic compounds: gingerol and shoagol have been broadly studied and these molecules have different properties, such as antipyretic, analgesic, angiogenesis inhibitor, immunomodulatory activities, among others. This review aims to present the components of ginger as well as its antagonistic effect on LPS, anti -inflammatory property and possible signaling pathway involved. The effect of ginger on lipopolysaccharide (LPS) consists in inhibiting the production of interleukin 12 (IL-12), resulting in reduced activation of macrophages induced by LPS; decreased expression of co-stimulatory molecules and MHC class II expression and reduced IL-2, impairing the activation and proliferation of CD4 + T cells. The anti-inflammatory property of the compound is associated with the ability to modulate T lymphocyte, in order to inhibit eosinophilia, reducing the amount of mast cells and inhibit the release

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[6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-κB in phorbol ester-stimulated mouse skin

Cited by 283 publications

References 55 publications

Synergistic Effects of Combined Phytochemicals and Skin Cancer Prevention in SENCAR Mice

Synergistic Effects of Combined Phytochemicals and Skin Cancer Prevention in SENCAR Mice

Urocortin increased endothelial ICAM1 by cPLA2-dependent NF-κB and PKA pathways in HUVECs

Efeito anti-inflamatório do gengibre e possível via de sinalização

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