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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)
417 Downloads (Pure)

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-kB. 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 profibrotic genes. In addition, mice treated with ANDRO showed reduced expression of inflammasome genes. Finally, ANDRO inhibited LPS-induced interleukin-1 beta expression through NF-kB 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-kB-dependent mechanism may be involved in the therapeutic effects of ANDRO.

Original languageEnglish
Article number3491
Number of pages12
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 14-Jun-2017

Keywords

  • FATTY LIVER-DISEASE
  • NF-KAPPA-B
  • NLRP3 INFLAMMASOME
  • FIBROSIS
  • INJURY
  • PANICULATA
  • MICE
  • BIOAVAILABILITY
  • EPIDEMIOLOGY
  • LIPOTOXICITY

Cite this