ABSTRACT
OBJECTIVE: Ginsenoside Re, a unique tetracyclic triterpenoid compound found in ginseng, has been suggested in previous reports to improve non-alcoholic fatty liver disease (NAFLD) by modulating lipid imbalance. This study aims to elucidate the potential mechanisms of Ginsenoside Re in treating NAFLD through a combination of bioinformatics analysis and biological experiments. METHODS: Network pharmacology methods were employed to systematically depict the effective components and mechanisms of Ginsenoside Re in improving NAFLD. Molecular docking was utilized to evaluate the binding affinity of Ginsenoside Re with NAFLD-related targets and identify potential targets. NAFLD-related target genes were obtained from the GEO database for gene enrichment analysis, revealing signaling pathways, biological processes, and gene differential expression. Finally, animal experiments were conducted to verify the mechanism of action of Ginsenoside Re in NAFLD. RESULTS: Network pharmacology analysis revealed that Ginsenoside Re improves NAFLD by modulating targets such as AKT1 and TLR4, findings corroborated by molecular docking, GEO database analysis, and experimental validation. Further investigation found that Ginsenoside Re ameliorates lipid metabolism disorders and inflammatory responses induced by NAFLD by modulating the PI3K/AKT and TLR4/NF-κB signaling pathways. CONCLUSION: Our study demonstrates the pharmacological effects of Ginsenoside Re in treating NAFLD, implicating multiple components, targets, and pathways. This provides a solid foundation for considering Ginsenoside Re as an alternative therapy for NAFLD, with promising clinical applications.
Subject(s)
Ginsenosides , Molecular Docking Simulation , Non-alcoholic Fatty Liver Disease , Signal Transduction , Ginsenosides/pharmacology , Ginsenosides/chemistry , Ginsenosides/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Male , Signal Transduction/drug effects , Mice, Inbred C57BL , Toll-Like Receptor 4/metabolism , Network Pharmacology , Mice , Humans , Lipid Metabolism/drug effects , Proto-Oncogene Proteins c-akt/metabolism , NF-kappa B/metabolism , Disease Models, Animal , Liver/drug effects , Liver/metabolism , Liver/pathologyABSTRACT
A convenient synthesis of novel 3-deoxy-5-hydroxy-1-aminocarbasugars was developed here. The benzyl-protected glucose-derived ketone 12 was selectively converted in high yield to enone 13via retro-Michael elimination of BnOH. The double bond of 13 was regio- and stereo-selectively reduced by the induction of C4-α-OBn to the multi-functionalized 15. 15 contained all the functionalities with similar configurations to carbasugars but with 3-H and 5-OH in the ring, and it would be a very interesting building block for organic synthesis or for bioactive compounds. As one application, 15 was further transformed into 1-amino-carbasugars by the reductive amination and final deprotection of benzyls. The targets were subjected to the in vitro inhibitory activity test against sucrase or maltase. The inhibitory activity of 17b, 17h or 17j against sucrase was nearly similar to that of voglibose. In comparison with voglibose, in vivo results similarly showed that 17b, 17h or 17j could lower the post-prandial blood glucose level after sucrose loading in healthy male ICR mice, while miglitol or acarbose was less effective. The molecular modeling study of some targets or voglibose with human sucrase could explain the inhibiting action.