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

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

Resultado de la investigación: Research - revisión exhaustivaArticle

Resumen

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.

IdiomaEnglish
Número de artículo3491
PublicaciónScientific Reports
Volumen7
Número de edición1
DOI
EstadoPublished - 1 dic 2017

Huella dactilar

Inflammasomes
Fatty Liver
Inflammation
andrographolide
Liver
Non-alcoholic Fatty Liver Disease
Hep G2 Cells
Choline
Triglycerides
Fibrosis
Fats
Amino Acids
Genes
Therapeutics
Therapeutic Uses
Alanine Transaminase
Interleukin-1beta
Histology
Anti-Inflammatory Agents
Macrophages

ASJC Scopus subject areas

  • General

Citar esto

Cabrera, Daniel ; Wree, Alexander ; Povero, Davide ; Solís, Nancy ; Hernandez, Alejandra ; Pizarro, Margarita ; Moshage, Han ; Torres, Javiera ; Feldstein, Ariel E. ; Cabello-Verrugio, Claudio ; Brandan, Enrique ; Barrera, Francisco ; Arab, Juan Pablo ; Arrese, Marco. / Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis. En: Scientific Reports. 2017 ; Vol. 7, N.º 1.
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title = "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 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.",
author = "Daniel Cabrera and Alexander Wree and Davide Povero and Nancy Solís and Alejandra Hernandez and Margarita Pizarro and Han Moshage and Javiera Torres and Feldstein, {Ariel E.} and Claudio Cabello-Verrugio and Enrique Brandan and Francisco Barrera and Arab, {Juan Pablo} and Marco Arrese",
year = "2017",
month = "12",
doi = "10.1038/s41598-017-03675-z",
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Cabrera, D, Wree, A, Povero, D, Solís, N, Hernandez, A, Pizarro, M, Moshage, H, Torres, J, Feldstein, AE, Cabello-Verrugio, C, Brandan, E, Barrera, F, Arab, JP & Arrese, M 2017, 'Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis' Scientific Reports, vol. 7, n.º 1, 3491. DOI: 10.1038/s41598-017-03675-z

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis. / Cabrera, Daniel; Wree, Alexander; Povero, Davide; Solís, Nancy; Hernandez, Alejandra; Pizarro, Margarita; Moshage, Han; Torres, Javiera; Feldstein, Ariel E.; Cabello-Verrugio, Claudio; Brandan, Enrique; Barrera, Francisco; Arab, Juan Pablo; Arrese, Marco.

En: Scientific Reports, Vol. 7, N.º 1, 3491, 01.12.2017.

Resultado de la investigación: Research - revisión exhaustivaArticle

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AU - Wree,Alexander

AU - Povero,Davide

AU - Solís,Nancy

AU - Hernandez,Alejandra

AU - Pizarro,Margarita

AU - Moshage,Han

AU - Torres,Javiera

AU - Feldstein,Ariel E.

AU - Cabello-Verrugio,Claudio

AU - Brandan,Enrique

AU - Barrera,Francisco

AU - Arab,Juan Pablo

AU - Arrese,Marco

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