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Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway.
- Source :
-
Lipids in health and disease [Lipids Health Dis] 2023 Dec 04; Vol. 22 (1), pp. 214. Date of Electronic Publication: 2023 Dec 04. - Publication Year :
- 2023
-
Abstract
- Background: Steatosis and inflammation are the hallmarks of nonalcoholic steatohepatitis (NASH). Rotundic acid (RA) is among the key triterpenes of Ilicis Rotundae Cortex and has exhibited multipronged effects in terms of lowering the lipid content and alleviating inflammation. The study objective is to systematically evaluate the potential mechanisms through which RA affects the development and progression of NASH.<br />Methods: Transcriptomic and proteomic analyses of primary hepatocytes isolated from the control, high-fat diet-induced NASH, and RA treatment groups were performed through Gene Ontology analysis and pathway enrichment. Hub genes were identified through network analysis. Integrative analysis revealed key RA-regulated pathways, which were verified by gene and protein expression studies and cell assays.<br />Results: Hub genes were identified and enriched in the Toll-like receptor 4 (TLR4)/activator protein-1 (AP1) signaling pathway and glycolysis pathway. RA reversed glycolysis and attenuated the TLR4/AP1 pathway, thereby reducing lipid accumulation and inflammation. Additionally, lactate release in L-02 cells increased with NaAsO <subscript>2</subscript> -treated and significantly decreased with RA treatment, thus revealing that RA had a major impact on glycolysis.<br />Conclusions: RA is effective in lowering the lipid content and reducing inflammation in mice with NASH by ameliorating glycolysis and TLR4/AP1 pathways, which contributes to the existing knowledge and potentially sheds light on the development of therapeutic interventions for patients with NASH.<br /> (© 2023. The Author(s).)
- Subjects :
- Humans
Mice
Animals
Liver metabolism
Transcription Factor AP-1 genetics
Transcription Factor AP-1 metabolism
Toll-Like Receptor 4 genetics
Toll-Like Receptor 4 metabolism
Proteomics
Signal Transduction genetics
Inflammation metabolism
Lipids
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease drug therapy
Non-alcoholic Fatty Liver Disease genetics
Non-alcoholic Fatty Liver Disease chemically induced
Triterpenes pharmacology
Triterpenes therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1476-511X
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Lipids in health and disease
- Publication Type :
- Academic Journal
- Accession number :
- 38049817
- Full Text :
- https://doi.org/10.1186/s12944-023-01976-z