| First Author | Kim K | Year | 2024 |
| Journal | J Ginseng Res | Volume | 48 |
| Issue | 1 | Pages | 89-97 |
| PubMed ID | 38223828 | Mgi Jnum | J:355698 |
| Mgi Id | MGI:7751501 | Doi | 10.1016/j.jgr.2023.10.001 |
| Citation | Kim K, et al. (2024) Ginsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor Coregulators. J Ginseng Res 48(1):89-97 |
| abstractText | BACKGROUND: Ginsenoside F2 (GF2), the protopanaxadiol-type constituent in Panax ginseng, has been reported to attenuate metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism of action is not fully understood. Here, this study investigates the molecular mechanism by which GF2 regulates MASLD progression through liver X receptor (LXR). METHODS: To demonstrate the effect of GF2 on LXR activity, computational modeling of protein-ligand binding, Time-resolved fluorescence resonance energy transfer (TR-FRET) assay for LXR cofactor recruitment, and luciferase reporter assay were performed. LXR agonist T0901317 was used for LXR activation in hepatocytes and macrophages. MASLD was induced by high-fat diet (HFD) feeding with or without GF2 administration in WT and LXRalpha(-/-) mice. RESULTS: Computational modeling showed that GF2 had a high affinity with LXRalpha. LXRE-luciferase reporter assay with amino acid substitution at the predicted ligand binding site revealed that the S264 residue of LXRalpha was the crucial interaction site of GF2. TR-FRET assay demonstrated that GF2 suppressed LXRalpha activity by favoring the binding of corepressors to LXRalpha while inhibiting the accessibility of coactivators. In vitro, GF2 treatments reduced T0901317-induced fat accumulation and pro-inflammatory cytokine expression in hepatocytes and macrophages, respectively. Consistently, GF2 administration ameliorated hepatic steatohepatitis and improved glucose or insulin tolerance in WT but not in LXRalpha(-/-) mice. CONCLUSION: GF2 alters the binding affinities of LXRalpha coregulators, thereby interrupting hepatic steatosis and inflammation in macrophages. Therefore, we propose that GF2 might be a potential therapeutic agent for the intervention in patients with MASLD. |
