ArticleBioconjugate chemistry2021
Dexamethasone and Fumaric Acid Ester Conjugate Synergistically Inhibits Inflammation and NF-κB in Macrophages.
Article in Bioconjugate chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 21 citations in OpenAlex.
- Identification and regulatory mechanism analysis of macrophage-related key genes in diabetic nephropathy.Diabetology & metabolic syndrome · 2026Article
- Blood Glucose and Triglyceride Changes Following the Administration of Commercial Enteral Nutrition Solutions with Differing Glucose and Fat Contents.Journal of the ASEAN Federation of Endocrine Societies · 2025Article
- NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting.Journal of cellular and molecular medicine · 2025Review
- Ketoconazole-Fumaric Acid Pharmaceutical Cocrystal: From Formulation Design for Bioavailability Improvement to Biocompatibility Testing and Antifungal Efficacy Evaluation.International journal of molecular sciences · 2024Article
- Article
- Glucocorticoids-based prodrug design: Current strategies and research progress.Asian journal of pharmaceutical sciences · 2024Review
- Immune exposure: how macrophages interact with the nucleus pulposus.Frontiers in immunology · 2023Review
- Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation.iScience · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophage-mediated inflammation drives autoimmune and chronic inflammatory diseases. Treatment with anti-inflammatory agents can be an effective strategy to reduce this inflammation; however, high concentrations of these agents can have immune-dampening and other serious side effects. Synergistic combination of anti-inflammatory agents can mitigate dosing by requiring less drug. Multiple anti-inflammatory agents were evaluated in combination for synergistic inhibition of macrophage inflammation. The most potent synergy was observed between dexamethasone (DXM) and fumaric acid esters (e.g., monomethyl fumarate (MMF)). Furthermore, this combination was found to synergistically inhibit inflammatory nuclear factor κB (NF-κB) transcription factor activity. The optimal ratio for synergy was determined to be 1:1, and DXM and MMF were conjugated by esterification at this molar ratio. The DXM-MMF conjugate displayed improved inhibition of inflammation over the unconjugated combination in both murine and human macrophages. In the treatment of human donor monocyte-derived macrophages, the combination of DXM and MMF significantly inhibited inflammatory gene expression downstream of NF-κB and overall performed better than either agent alone. Further, the DXM-MMF conjugate significantly inhibited expression of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome-associated genes. The potent anti-inflammatory activity of the DXM-MMF conjugate in human macrophages indicates that it may have benefits in the treatment of autoimmune and inflammatory diseases.
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Registered trials
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