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Physcion 8-O-β-glucopyranoside ameliorates liver fibrosis through inflammation inhibition by regulating SIRT3-mediated NF-κB P65 nuclear expression.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2021 Jan; Vol. 90, pp. 107206. Date of Electronic Publication: 2020 Nov 25. - Publication Year :
- 2021
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Abstract
- Physcion 8-O-β-glucopyranoside (PSG), an anthraquinone extracted from Rumex japonicus Houtt, has various pharmacological effects, however, the effect of PSG on liver fibrosis and its related mechanism remain to be determined. We here showed that PSG ameliorated liver injury and liver fibrosis, decreased collagen deposition and inhibited inflammation in carbon tetrachloride (CCl <subscript>4</subscript> )-induced rats. Consistent with the in vivo results, PSG suppressed the transforming growth factor-β1 (TGF-β1)-induced cell viability, liver fibrosis and secretion of inflammatory factors in hepatic stellate cells (HSCs). Interestingly, PSG increased the enzyme activity and promoter activity of sirtuin 3 (SIRT3) in fibrotic liver and activated HSCs. In addition, PSG notably increased the mRNA and protein expression of SIRT3 both in vivo and in vitro. Depletion of SIRT3 either by using 3-TYP (SIRT3 selective inhibitor) or SIRT3 siRNA attenuated the anti-inflammatory effect of PSG in activated HSCs. Further study found that TGF-β1 increased the nuclear expression of NF-κB p65, but showed no obvious effect on the total NF-κB p65 expression. Compared to the control adenovirus (Ad.mk), overexpression of SIRT3 by infecting adenovirus encoding SIRT3 (Ad.SIRT3) notably decreased the nuclear expression of NF-κB p65 in activated HSCs. Our results demonstrated that PSG attenuated inflammation by regulating SIRT3-mediated NF-κB P65 nuclear expression in liver fibrosis, providing novel molecular insights into the anti-fibrotic effect of PSG.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Carbon Tetrachloride
Cells, Cultured
Chemical and Drug Induced Liver Injury enzymology
Chemical and Drug Induced Liver Injury pathology
Collagen metabolism
Emodin pharmacology
Hepatic Stellate Cells drug effects
Hepatic Stellate Cells metabolism
Hepatic Stellate Cells pathology
Liver enzymology
Liver pathology
Liver Cirrhosis, Experimental chemically induced
Liver Cirrhosis, Experimental enzymology
Liver Cirrhosis, Experimental pathology
Male
Rats, Sprague-Dawley
Signal Transduction
Sirtuins genetics
Rats
Anti-Inflammatory Agents pharmacology
Chemical and Drug Induced Liver Injury prevention & control
Emodin analogs & derivatives
Glucosides pharmacology
Liver drug effects
Liver Cirrhosis, Experimental prevention & control
Sirtuins metabolism
Transcription Factor RelA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 90
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33246826
- Full Text :
- https://doi.org/10.1016/j.intimp.2020.107206