Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway
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 obj...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-023-01976-z |
| _version_ | 1797397847269703680 |
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| author | Xing-Yang Shi Xiao-Min Zheng Hui-Jie Liu Xue Han Lei Zhang Bei Hu Shan Li |
| author_facet | Xing-Yang Shi Xiao-Min Zheng Hui-Jie Liu Xue Han Lei Zhang Bei Hu Shan Li |
| author_sort | Xing-Yang Shi |
| collection | DOAJ |
| description | 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. 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. 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 NaAsO2-treated and significantly decreased with RA treatment, thus revealing that RA had a major impact on glycolysis. 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. |
| first_indexed | 2024-03-09T01:16:06Z |
| format | Article |
| id | doaj.art-e82101d7f5944719a66ac7b7c7af792e |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-03-09T01:16:06Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-e82101d7f5944719a66ac7b7c7af792e2023-12-10T12:29:55ZengBMCLipids in Health and Disease1476-511X2023-12-0122111810.1186/s12944-023-01976-zRotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathwayXing-Yang Shi0Xiao-Min Zheng1Hui-Jie Liu2Xue Han3Lei Zhang4Bei Hu5Shan Li6MOE International Joint Laboratory for Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of TechnologyMOE International Joint Laboratory for Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of TechnologyMOE International Joint Laboratory for Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of TechnologyMOE International Joint Laboratory for Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of TechnologyMOE International Joint Laboratory for Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of TechnologyDepartment of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityMOE International Joint Laboratory for Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of TechnologyAbstract 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. 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. 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 NaAsO2-treated and significantly decreased with RA treatment, thus revealing that RA had a major impact on glycolysis. 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.https://doi.org/10.1186/s12944-023-01976-zNASHRAGlycolysisTLR4/AP1ProteomicsTranscriptomics |
| spellingShingle | Xing-Yang Shi Xiao-Min Zheng Hui-Jie Liu Xue Han Lei Zhang Bei Hu Shan Li Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway Lipids in Health and Disease NASH RA Glycolysis TLR4/AP1 Proteomics Transcriptomics |
| title | Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway |
| title_full | Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway |
| title_fullStr | Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway |
| title_full_unstemmed | Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway |
| title_short | Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway |
| title_sort | rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the tlr4 ap1 signaling pathway |
| topic | NASH RA Glycolysis TLR4/AP1 Proteomics Transcriptomics |
| url | https://doi.org/10.1186/s12944-023-01976-z |
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