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Type: Artigo de periódico
Title: (+)-Altholactone exhibits broad spectrum immune modulating activity by inhibiting the activation of pro-inflammatory cytokines in RAW 264.7 cell lines
Author: Johnson, TA
Sohn, J
Ward, AE
Cohen, TL
Lorig-Roach, ND
Chen, HX
Pilli, RA
Widjaja, EA
Hanafi, M
Kardono, LBS
Lotulung, PD
Boundy-Mills, K
Bjeldanes, LF
Abstract: An 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.
Subject: Styryl lactones
I kappa B alpha
IL-1 beta
Country: Inglaterra
Editor: Pergamon-elsevier Science Ltd
Citation: Bioorganic & Medicinal Chemistry. Pergamon-elsevier Science Ltd, v. 21, n. 14, n. 4358, n. 4364, 2013.
Rights: fechado
Identifier DOI: 10.1016/j.bmc.2013.04.055
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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