Author:
Shi Xing-Yang,Zheng Xiao-Min,Liu Hui-Jie,Han Xue,Zhang Lei,Hu Bei,Li Shan
Abstract
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.
Funder
National Key R&D Projects
Guangdong Provincial Medical Products Administration
Special Project for Research and Development in Key areas of Guangdong Province
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province for Distinguished Young Scholars
High-level Hospital Construction Project of Guangdong Provincial People’s Hospital
Basic and Applied Basic Research Foundation of Guangdong Province
Publisher
Springer Science and Business Media LLC
Subject
Biochemistry (medical),Clinical Biochemistry,Endocrinology,Endocrinology, Diabetes and Metabolism