Gastrodin attenuates rheumatoid arthritis by targeting KAT8 to inhibit the lactylation of H3K9 DOI Creative Commons

Yufang Dai,

Shunshun Wang,

Jiayi Luo

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction, with limited therapeutic options. This study investigated the potential of gastrodin (GAS), natural phenolic glycoside derived from Gastrodia elata, in targeting lysine acetyltransferase 8 (KAT8) to suppress histone H3K9 lactylation (H3K9la), novel post-translational modification linked inflammatory responses. Methods: The effect GAS on RA was verified constructing models vivo vitro . Molecular docking, surface plasmon resonance (SPR) assays, overexpression silencing experiments were used verify results. Results: In demonstrated that (10–20 μM) significantly inhibited lipopolysaccharide (LPS)-induced expression pro-inflammatory cytokines (IL-6, MMP1, MMP13) fibroblast-like synoviocytes (FLS) THP-1 macrophages downregulating glycolysis lactate production. docking assays confirmed KAT8 as direct target GAS, dissociation constant ( K D ) 413.72 μM. Overexpression revealed destabilized KAT8, thereby reducing H3K9la levels. , (20 mg/kg) ameliorated swelling hyperplasia Sprague-Dawley rat adjuvant-induced (AIA) model, correlating decreased IL-6 expression. Discussion: These findings establish promising agent for modulating KAT8-mediated lactylation, providing new insights into epigenetic regulation inflammation.

Language: Английский

Gastrodin attenuates rheumatoid arthritis by targeting KAT8 to inhibit the lactylation of H3K9 DOI Creative Commons

Yufang Dai,

Shunshun Wang,

Jiayi Luo

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction, with limited therapeutic options. This study investigated the potential of gastrodin (GAS), natural phenolic glycoside derived from Gastrodia elata, in targeting lysine acetyltransferase 8 (KAT8) to suppress histone H3K9 lactylation (H3K9la), novel post-translational modification linked inflammatory responses. Methods: The effect GAS on RA was verified constructing models vivo vitro . Molecular docking, surface plasmon resonance (SPR) assays, overexpression silencing experiments were used verify results. Results: In demonstrated that (10–20 μM) significantly inhibited lipopolysaccharide (LPS)-induced expression pro-inflammatory cytokines (IL-6, MMP1, MMP13) fibroblast-like synoviocytes (FLS) THP-1 macrophages downregulating glycolysis lactate production. docking assays confirmed KAT8 as direct target GAS, dissociation constant ( K D ) 413.72 μM. Overexpression revealed destabilized KAT8, thereby reducing H3K9la levels. , (20 mg/kg) ameliorated swelling hyperplasia Sprague-Dawley rat adjuvant-induced (AIA) model, correlating decreased IL-6 expression. Discussion: These findings establish promising agent for modulating KAT8-mediated lactylation, providing new insights into epigenetic regulation inflammation.

Language: Английский

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