Dataset Information

Ginsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor Coregulators.

ABSTRACT:

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 LXRα^-/- mice.

Results

Computational modeling showed that GF2 had a high affinity with LXRα. LXRE-luciferase reporter assay with amino acid substitution at the predicted ligand binding site revealed that the S264 residue of LXRα was the crucial interaction site of GF2. TR-FRET assay demonstrated that GF2 suppressed LXRα activity by favoring the binding of corepressors to LXRα 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 LXRα^-/- mice.

Conclusion

GF2 alters the binding affinities of LXRα 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.

SUBMITTER: Kim K

PROVIDER: S-EPMC10785242 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Ginsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor Coregulators.

Kim Kyurae K Kim Myung-Ho MH Kang Ji In JI Baek Jong-In JI Jeon Byeong-Min BM Kim Ho Min HM Kim Sun-Chang SC Jeong Won-Il WI

Journal of ginseng research 20231027 1

<h4>Background</h4>Ginsenoside F2 (GF2), the protopanaxadiol-type constituent in <i>Panax ginseng</i>, 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).<h4>Methods</h4>To demonstrate the effect of GF2 on LXR activity, computational modeling of protein-ligand binding, ...[more]

PMID: 38223828

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Dataset Information

Ginsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor Coregulators.

Background

Methods

Results

Conclusion

Publications

Ginsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor Coregulators.

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