Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

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dc.contributor.authorCabrera, D.
dc.contributor.authorWree, A.
dc.contributor.authorPovero, D.
dc.contributor.authorSolís, N.
dc.contributor.authorHernandez, A.
dc.contributor.authorPizarro, M.
dc.contributor.authorMoshage, H.
dc.contributor.authorTorres, J.
dc.contributor.authorFeldstein, A.E.
dc.contributor.authorCabello-Verrugio, C.
dc.contributor.authorBrandan, E.
dc.contributor.authorBarrera, F.
dc.contributor.authorArab, J.P.
dc.contributor.authorArrese, M.
dc.date.accessioned2017-11-24T18:04:47Z
dc.date.available2017-11-24T18:04:47Z
dc.date.issued2017-06
dc.descriptionIndexación: Scopus.es_CL
dc.description.abstractTherapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-Amino-Acid-defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-Times/week). Also, we assessed serum levels of alanine-Aminotransferase (ALT), liver histology, hepatic triglyceride content (HTC) and hepatic expression of pro-inflammatory, pro-fibrotic and inflammasome genes. Inflammasome activation was also evaluated in fat-laden HepG2 cells. Our results showed that ANDRO administration decreased HTC and attenuated hepatic inflammation and fibrosis in CDAA-fed mice. ANDRO treatment determined a strong reduction in hepatic macrophage infiltration and reduced hepatic mRNA levels of both pro-inflammatory and pro-fibrotic genes. In addition, mice treated with ANDRO showed reduced expression of inflammasome genes. Finally, ANDRO inhibited LPS-induced interleukin-1β expression through NF-κB inhibition in fat-laden HepG2 cells and inflammasome disassembly. In conclusion, ANDRO administration reduces inflammation and fibrosis in experimental NASH. Inflammasome modulation by a NF-κB-dependent mechanism may be involved in the therapeutic effects of ANDRO.es_CL
dc.description.urihttps://www.nature.com/articles/s41598-017-03675-z
dc.identifier.citationScientific Reports. Volume 7, Issue 1, 1 December 2017, Article number 3491es_CL
dc.identifier.issn2045-2322
dc.identifier.otherDOI: 10.1038/s41598-017-03675-z
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/4736
dc.language.isoenes_CL
dc.publisherNature Publishing Groupes_CL
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectFATTY LIVER-DISEASEes_CL
dc.subjectNF-KAPPA-Bes_CL
dc.subjectNLRP3 INFLAMMASOMEes_CL
dc.subjectFIBROSISes_CL
dc.subjectINJURYes_CL
dc.subjectPANICULATAes_CL
dc.subjectMICEes_CL
dc.subjectBIOAVAILABILITYes_CL
dc.subjectEPIDEMIOLOGYes_CL
dc.subjectLIPOTOXICITYes_CL
dc.titleAndrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitises_CL
dc.typeArtículoes_CL
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