ArticleMolecular medicine (Cambridge, Mass.)2025
Sodium butyrate regulates macrophage polarization by TGR5/β-arrestin2 in vitro.
Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- The Bile Acid Signaling Axis: Deciphering the Roles of FXR and TGR5 in Hepatic Steatosis, Fibrosis, and Cancer.Pharmacology research & perspectives · 2026Review
- Isoorientin attenuates aging-induced bone deterioration by suppressing M1-mediated TLR4-MAPK-NF-κB inflammatory signaling.Biogerontology · 2026Article
- Metabolic messengers from the gut to the joint: Toward precision management of osteoarthritis (Review).International journal of molecular medicine · 2026Review
- Rational Design and Evaluation of Novel TGR5 Agonists for Diabetes.Molecules (Basel, Switzerland) · 2026Article
- Gut microbiota drives the metabolic dysregulation in obesity-prone individuals by impairing GDCA-mediated activation of brown adipose thermogenesis and ileal GLP-1 secretion.Acta pharmaceutica Sinica. B · 2026Article
- Research Progress on the Mechanism and Targeted Intervention of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1)-Mediated "Inflammation-Apoptosis-Metabolism-Microcirculation" Regulatory Network in Hepatitis B-Associated Liver Failure.Drug design, development and therapy · 2026Review
- Macrophages in Ulcerative Colitis: Immunomodulatory Roles, Phenotypic Switching, and Therapeutic Targeting.Journal of innate immunity · 2026Review
- Role of intestinal SCFAs homeostasis in the hepatoprotective effect of Clostridium butyricum in T2DM.NPJ biofilms and microbiomes · 2025Article
- Type 2 Diabetes and the Multifaceted Gut-X Axes.Nutrients · 2025Review
- Multi-omics profiling identifies M1 macrophage polarization-associated biomarkers in hepatitis B virus-related acute-on-chronic liver failure.Frontiers in microbiology · 2025Article
- Unraveling the Gut-Liver-Brain Axis: Microbiome, Inflammation, and Emerging Therapeutic Approaches.Mediators of inflammation · 2025Review
- Cimifugin ameliorates ulcerative colitis-related lung injury by modulating the JAK1/STAT1 signaling pathway and macrophage M1 polarization.Frontiers in immunology · 2025Article
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6 authors.
Funding
Abstract
backgroundMacrophages play an important role in the pathogenesis of ulcerative colitis (UC). We will explore the effects of sodium butyrate (SB) on macrophage function.
methodsThe targets of butyric acid were identified using SwissTargetPrediction database and surface plasmon resonance (SPR). Limited proteolysis mass spectrometry (Lip-MS) was used to further investigate the binding sites of butyric acid with its targets and molecular docking was employed to simulate their binding modes. Macrophage polarization model was established with lipopolysaccharide (LPS) in vitro. Takeda G protein-coupled receptor 5 (TGR5) and β-arrestin2 expression and macrophage polarization markers were detected with or without SB.
resultsTGR5 was identified as the target of butyric acid. Moreover, the amino acid regions 275-286 and 321-330 of TGR5 (GPBAR1 [275-286] and GPBAR1 [321-330]) were the potential binding regions for butyric acid. Based on molecular docking analysis, butyric acid formed effective hydrogen-bonding interactions with ASP-284 and TYR-287 of TGR5. In cell experiments, LPS inhibited the expression of TGR5, β-arrestin2, IL-10, ARG1, and CD206 and increased the expression of IL-1β, iNOS, and CD86, while SB reversed the effect of LPS. SBI-115, a TGR5 antagonist, and knockdown of β-arrestin2 inhibited the effect of sodium butyrate. INT-777, a TGR5 agonist, reversed the inhibitory effect of knockdown of β-arrestin2.
conclusionSB inhibited M1-like polarization and promoted M2-like polarization induced by LPS via TGR5/β-arrestin2 in RAW264.7 cells and TGR5 was the target of SB.
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