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

Abstract 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 eva...

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Autores principales:	Daniel Cabrera, Alexander Wree, Davide Povero, Nancy Solís, Alejandra Hernandez, Margarita Pizarro, Han Moshage, Javiera Torres, Ariel E. Feldstein, Claudio Cabello-Verrugio, Enrique Brandan, Francisco Barrera, Juan Pablo Arab, Marco Arrese
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bd86bebf1d174a5fad6317ffa6d68f10
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spelling	oai:doaj.org-article:bd86bebf1d174a5fad6317ffa6d68f102021-12-02T12:32:07ZAndrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis10.1038/s41598-017-03675-z2045-2322https://doaj.org/article/bd86bebf1d174a5fad6317ffa6d68f102017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03675-zhttps://doaj.org/toc/2045-2322Abstract 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.Daniel CabreraAlexander WreeDavide PoveroNancy SolísAlejandra HernandezMargarita PizarroHan MoshageJaviera TorresAriel E. FeldsteinClaudio Cabello-VerrugioEnrique BrandanFrancisco BarreraJuan Pablo ArabMarco ArreseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel Cabrera Alexander Wree Davide Povero Nancy Solís Alejandra Hernandez Margarita Pizarro Han Moshage Javiera Torres Ariel E. Feldstein Claudio Cabello-Verrugio Enrique Brandan Francisco Barrera Juan Pablo Arab Marco Arrese Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis
description	Abstract 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.
format	article
author	Daniel Cabrera Alexander Wree Davide Povero Nancy Solís Alejandra Hernandez Margarita Pizarro Han Moshage Javiera Torres Ariel E. Feldstein Claudio Cabello-Verrugio Enrique Brandan Francisco Barrera Juan Pablo Arab Marco Arrese
author_facet	Daniel Cabrera Alexander Wree Davide Povero Nancy Solís Alejandra Hernandez Margarita Pizarro Han Moshage Javiera Torres Ariel E. Feldstein Claudio Cabello-Verrugio Enrique Brandan Francisco Barrera Juan Pablo Arab Marco Arrese
author_sort	Daniel Cabrera
title	Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis
title_short	Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis
title_full	Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis
title_fullStr	Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis
title_full_unstemmed	Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis
title_sort	andrographolide ameliorates inflammation and fibrogenesis and attenuates inflammasome activation in experimental non-alcoholic steatohepatitis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bd86bebf1d174a5fad6317ffa6d68f10
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Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

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