Scientific reports, 2017-06, Vol.7 (1), p.3491-12, Article 3491
2017
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- Autor(en) / Beteiligte
- Titel
- Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis
- Ist Teil von
- Scientific reports, 2017-06, Vol.7 (1), p.3491-12, Article 3491
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2017
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-017-03675-zTitel-ID: cdi_doaj_primary_oai_doaj_org_article_bd86bebf1d174a5fad6317ffa6d68f10
- Format
- –
- Schlagworte
- Alanine, Animals, Anti-inflammatory agents, Anti-Inflammatory Agents, Non-Steroidal - administration & dosage, Cells, Cultured, Choline, Diterpenes - administration & dosage, Fibrosis, Fibrosis - prevention & control, Inflammasomes, Inflammasomes - metabolism, Inflammation, Inflammation - complications, Inflammation - metabolism, Inflammation - prevention & control, Lipopolysaccharides, Liver, Macrophages, Macrophages - drug effects, Male, Mice, Inbred C57BL, mRNA, NF-kappa B - metabolism, NF-κB protein, Non-alcoholic Fatty Liver Disease - complications, Rats, Wistar, Rodents, Serum levels, Transcription activation