Guggulsterone, a plant sterol, inhibits NF-κB activation and protects pancreatic β cells from cytokine toxicity

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dc.contributor.authorLv, Nako
dc.contributor.authorSong, Mi-Youngko
dc.contributor.authorKim, Eun-Kyungko
dc.contributor.authorPark, Jin-Wooko
dc.contributor.authorKwon, Kang-Beomko
dc.contributor.authorPark, Byung-Hyunko
dc.date.accessioned2024-03-22T06:03:58Z-
dc.date.available2024-03-22T06:03:58Z-
dc.date.created2024-03-21-
dc.date.issued2008-07-
dc.identifier.citationMOLECULAR AND CELLULAR ENDOCRINOLOGY, v.289, no.1-2, pp.49 - 59-
dc.identifier.issn0303-7207-
dc.identifier.urihttp://hdl.handle.net/10203/318761-
dc.description.abstractGuggulsterone has been used to treat hyperlipidemia, arthritis, and obesity. Although its anti-inflammatory and anti-hyperlipidemic effects have been well documented, the effect of guggulsterone on pancreatic P cells is unknown. Therefore, in this study, the effect of guggulsterone on IL-1 beta-and IFN-gamma-induced beta-cell damage was investigated. Treatment of RINm5F (RIN) rat insulinoma cells with IL-1 beta and IFN-gamma induced cell damage, and this damage was well correlated with nitric oxide (NO) and prostaglandin E-2 (PGE(2)) production. However, guggulsterone completely prevented cytokines-mediated cytotoxicity, as well as NO and PGE(2) production, and these effects were correlated with reduced levels of the inducible form of NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein expressions. The molecular mechanism by which guggulsterone inhibits iNOS and COX-2 gene expressions appeared to involve the inhibition of NF-kappa B activation. The cytoprotective effects of guggulsterone were also mediated through the suppression of the JAK/STAT pathway. Cells treated with the cytokines downregulated the protein level of SOCS-3, however pretreatment with guggulsterone attenuated this decrease. Additionally, in a second set of experiments in which rat islets were used, the findings regarding the beta-cell protective effects of guggulsterone were essentially the same as those observed when RIN cells were used; guggulsterone prevented cytokines-induced NO and PGE(2) production, iNOS and COX-2 expressions, JAK/STAT activation, NF-kappa B activation, downregulation of SOCS-3, and impairment of glucose-stimulated insulin secretion. Collectively, these results suggest that guggulsterone may be used to preserve functional beta-cell mass. (C) 2008 Elsevier Ireland Ltd. All rights reserved.-
dc.languageEnglish-
dc.publisherELSEVIER IRELAND LTD-
dc.titleGuggulsterone, a plant sterol, inhibits NF-κB activation and protects pancreatic β cells from cytokine toxicity-
dc.typeArticle-
dc.identifier.wosid000257841700007-
dc.identifier.scopusid2-s2.0-45049087913-
dc.type.rimsART-
dc.citation.volume289-
dc.citation.issue1-2-
dc.citation.beginningpage49-
dc.citation.endingpage59-
dc.citation.publicationnameMOLECULAR AND CELLULAR ENDOCRINOLOGY-
dc.identifier.doi10.1016/j.mce.2008.02.001-
dc.contributor.localauthorPark, Byung-Hyun-
dc.contributor.nonIdAuthorLv, Na-
dc.contributor.nonIdAuthorSong, Mi-Young-
dc.contributor.nonIdAuthorKim, Eun-Kyung-
dc.contributor.nonIdAuthorPark, Jin-Woo-
dc.contributor.nonIdAuthorKwon, Kang-Beom-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorguggulsterone-
dc.subject.keywordAuthorcytokine-
dc.subject.keywordAuthorbeta cells-
dc.subject.keywordAuthorNF-kappa B-
dc.subject.keywordAuthorSTAT-
dc.subject.keywordAuthorSOCS-3-
dc.subject.keywordPlusNITRIC-OXIDE SYNTHASE-
dc.subject.keywordPlusFARNESOID-X-RECEPTOR-
dc.subject.keywordPlusNATURAL-PRODUCT GUGGULSTERONE-
dc.subject.keywordPlusJAK-STAT-
dc.subject.keywordPlusMEDIATED TOXICITY-
dc.subject.keywordPlusSIGNAL-TRANSDUCTION-
dc.subject.keywordPlusINSULIN-SECRETION-
dc.subject.keywordPlusHUMAN ISLETS-
dc.subject.keywordPlusC-JUN-
dc.subject.keywordPlusEXPRESSION-
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