Cabrera, D.Wree, A.Povero, D.Solís, N.Hernandez, A.Pizarro, M.Moshage, H.Torres, J.Feldstein, A.E.Cabello-Verrugio, C.Brandan, E.Barrera, F.Arab, J.P.Arrese, M.2017-11-242017-11-242017-06Scientific Reports. Volume 7, Issue 1, 1 December 2017, Article number 34912045-2322DOI: 10.1038/s41598-017-03675-zhttp://repositorio.unab.cl/xmlui/handle/ria/4736Indexación: Scopus.Therapy 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.enFATTY LIVER-DISEASENF-KAPPA-BNLRP3 INFLAMMASOMEFIBROSISINJURYPANICULATAMICEBIOAVAILABILITYEPIDEMIOLOGYLIPOTOXICITYArtículo