(+)-Altholactone exhibits broad spectrum immune modulating activity by inhibiting the activation of pro-inflammatory cytokines in RAW 264.7 cell lines

dc.creatorJohnson, TA
dc.creatorSohn, J
dc.creatorWard, AE
dc.creatorCohen, TL
dc.creatorLorig-Roach, ND
dc.creatorChen, HX
dc.creatorPilli, RA
dc.creatorWidjaja, EA
dc.creatorHanafi, M
dc.creatorKardono, LBS
dc.creatorLotulung, PD
dc.creatorBoundy-Mills, K
dc.creatorBjeldanes, LF
dc.date2013
dc.date42186
dc.date2014-07-30T13:38:33Z
dc.date2015-11-26T16:33:05Z
dc.date2014-07-30T13:38:33Z
dc.date2015-11-26T16:33:05Z
dc.date.accessioned2018-03-28T23:14:46Z
dc.date.available2018-03-28T23:14:46Z
dc.identifierBioorganic & Medicinal Chemistry. Pergamon-elsevier Science Ltd, v. 21, n. 14, n. 4358, n. 4364, 2013.
dc.identifier0968-0896
dc.identifierWOS:000320838200043
dc.identifier10.1016/j.bmc.2013.04.055
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/52424
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/52424
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1270722
dc.descriptionAn evaluation of Indonesian plants to identify compounds with immune modulating activity revealed that the methanolic extract of an Alphonsea javanica Scheff specimen possessed selective anti-inflammatory activity in a nuclear factor-kappa B (NF-kappa B) luciferase and MTT assay using transfected macrophage immune (Raw264.7) cells. A high-throughput LC/MS-ELSD based library approach of the extract in combination with the NF-kappa B and MTT assays revealed the styryl lactone (+)-altholactone (2) was responsible for the activity. Compound 2, its acetylated derivate (+)-3-O-acetylaltholactone (3), and the major compound of this class, (+)-goniothalmin (1), were further evaluated to determine their anti-inflammatory potential in the NF-kappa B assay. Concentration-response studies of 1-3 indicated that only 2 possessed NF-kappa B based anti-inflammatory activity. Compound 2 reduced the LPS-induced NO production, phosphorylation of I kappa B alpha, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using Western blot analysis. Further studies using qPCR indicated 2 reduced the expression of eight pro-inflammatory cytokines/enzymes (0.8-5.0 mu M) which included: COX-2, iNOS, IP-10, IL-1 beta, MCP-1, GCS-F, IL-6 and IFN-beta. These results indicated that 2 displays broad spectrum immune modulating activity by functioning as an anti-inflammatory agent against LPS-induced NF-kappa B signaling. Conversely the selective cytotoxicity and in vivo anti-tumor and anti-inflammatory activity previously reported for 1 do not appear to arise from a mechanism that is linked to the NF-kappa B immune mediated pathway. (C) 2013 Published by Elsevier Ltd.
dc.description21
dc.description14
dc.description4358
dc.description4364
dc.descriptionFogarty International Center [U01TW008160]
dc.descriptionOffice of Dietary Supplements
dc.descriptionNational Science Foundation
dc.descriptionDepartment of Energy
dc.descriptionUSDA Agricultural Food Research Initiative of the National Institute of Food and Agriculture, USDA [35621-04750]
dc.descriptionNIH-MARC [GM007910-31]
dc.descriptionFogarty International Center [U01TW008160]
dc.descriptionUSDA Agricultural Food Research Initiative of the National Institute of Food and Agriculture, USDA [35621-04750]
dc.descriptionNIH-MARC [GM007910-31]
dc.languageen
dc.publisherPergamon-elsevier Science Ltd
dc.publisherOxford
dc.publisherInglaterra
dc.relationBioorganic & Medicinal Chemistry
dc.relationBioorg. Med. Chem.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectStyryl lactones
dc.subject(+)-Altholactone
dc.subject(+)-Goniothalamin
dc.subjectAnti-inflammatory
dc.subjectNF-kB
dc.subjectqPCR
dc.subjectNO
dc.subjectI kappa B alpha
dc.subjectiNOS
dc.subjectCOX-2
dc.subjectIP-10
dc.subjectIL-1 beta
dc.subjectMCP-1
dc.subjectGCS-F
dc.subjectIL-6
dc.subjectIFN-beta
dc.subjectNf-kappa-b
dc.subjectOxidative Stress
dc.subjectStyryl-lactones
dc.subjectCancer-cells
dc.subjectGoniothalamin
dc.subjectAltholactone
dc.subjectApoptosis
dc.subjectTumor
dc.subjectLeads
dc.title(+)-Altholactone exhibits broad spectrum immune modulating activity by inhibiting the activation of pro-inflammatory cytokines in RAW 264.7 cell lines
dc.typeArtículos de revistas


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