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Naringenin alleviates nonalcoholic steatohepatitis in middle-aged Apoe -/- mice: role of SIRT1.
- Source :
-
Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2021 Jan; Vol. 81, pp. 153412. Date of Electronic Publication: 2020 Nov 18. - Publication Year :
- 2021
-
Abstract
- Background: Naringenin is naturally isolated from citrus fruits possessing many pharmacological activities. However, little is known about the effect of naringenin on nonalcoholic steatohepatitis (NASH) in the model of metabolic syndrome.<br />Purpose: The present study is aimed to investigate the effect of naringenin on NASH in 12-mo-old male ApoE <superscript>-/-</superscript> mice and its possible underlying mechanism.<br />Methods: In vivo, 12-mo-old male ApoE <superscript>-/-</superscript> mice were administrated with naringenin by intragastric gavage for 12 weeks. At the end of experiment, the blood samples and liver tissues were collected. Metabolic parameters in serum, levels of triglyceride, cholesterol and hydroxyproline, activities of antioxidant enzymes, and content of inflammatory cytokines (TNF-α and IL-6) in liver were examined by corresponding assay kits. Pathological changes in liver were observed by hematoxylin-eosin, oil red O, masson's trichrome, picro-sirius red and senescence β-galactosidase staining. Dihydroethidium was used for detection of reactive oxygen species (ROS). In vitro, AML-12 cells were treated with oleic acid in the presence or absence of naringenin for 24 h. Transfection of SIRT1 siRNA was also conducted in vitro. Lipid accumulation, cellular ROS generation, malondialdehyde content, antioxidant enzyme activities and secretion levels of TNF-α and IL-6 were examined. Both in vivo and in vitro, gene expressions were detected by real-time PCR or western blot.<br />Results: Naringenin administration improved metabolic parameters, suppressed hepatic steatosis, regulated expression of genes involved in lipid metabolism (FASN, SCD1, PPARα and CPT1α), reduced hepatic fibrosis and cell senescence, inhibited hepatic inflammation as evidenced by the decreased macrophage recruitment and content of TNF-α and IL-6, and reduced hepatic oxidative stress by suppressing ROS generation and normalizing activities of antioxidant enzymes. Notably, naringenin administration increased hepatic SIRT1 protein expression and activity along with the increased deacetylation of liver kinase B1 (LKB1), PGC1α and NF-κB. In vitro study, the benefits of naringenin on lipid accumulation, oxidative stress and inflammation were diminished by SIRT1 siRNA transfection.<br />Conclusions: These results indicate that naringenin administration may be a potential curative therapy for NASH treatment and the activation of hepatic SIRT1-mediated signaling cascades is involved in its beneficial effects.<br /> (Copyright © 2020. Published by Elsevier GmbH.)
- Subjects :
- Animals
Lipid Metabolism drug effects
Liver drug effects
Liver pathology
Liver Cirrhosis drug therapy
Liver Cirrhosis pathology
Male
Mice, Inbred C57BL
Mice, Knockout, ApoE
NF-kappa B metabolism
Non-alcoholic Fatty Liver Disease metabolism
Non-alcoholic Fatty Liver Disease pathology
Nuclear Proteins metabolism
Oxidative Stress drug effects
Reactive Oxygen Species metabolism
Transcription Factors metabolism
Mice
Flavanones pharmacology
Non-alcoholic Fatty Liver Disease drug therapy
Sirtuin 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1618-095X
- Volume :
- 81
- Database :
- MEDLINE
- Journal :
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33234364
- Full Text :
- https://doi.org/10.1016/j.phymed.2020.153412