ArticleBritish journal of pharmacology2023
Soluble epoxide hydrolase inhibition enhances production of specialized pro-resolving lipid mediator and promotes macrophage plasticity.
Article in British journal of pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 36 citations in OpenAlex.
- Lipid Metabolic Reprogramming in Periodontitis-Associated Alveolar Bone Remodeling: Mechanisms, Signaling Pathways, and Therapeutic Implications.Biomolecules · 2026Review
- Aging and periodontitis increase brain dissemination of oral bacteria.Journal of periodontology · 2026Article
- B10 Adoptive Transfer Ameliorates Inflammation and Bone Loss in Experimental Periodontitis Through Promoting Macrophage-Mediated Pro-Resolving Functions.Inflammation · 2026Article
- Downregulation of osteoclast differentiation and activation by the soluble epoxide hydrolase inhibition.The Journal of pharmacology and experimental therapeutics · 2026Article
- Soluble epoxide hydrolase inhibition restores pro-resolving lipid mediators and reduces inflammation in localized provoked vulvodynia.Frontiers in pharmacology · 2026Article
- Ferroptosis and macrophage efferocytosis in periodontitis: Biological insights and therapeutic advances.Virulence · 2025Review
- A cautionary tale: Non-steroidal anti-inflammatory drug use and localized provoked vulvodynia.The journal of pain · 2025Article
- Bioactive constituents isolated from the leaves of Phyllostachys Bambusoides with potent soluble epoxide hydrolase inhibitory activity: enzyme kinetics, molecular docking, and molecular dynamics simulations.Journal of computer-aided molecular design · 2025Article
- Alterations of Bioactive Lipid Profiles in the Retina Following Traumatic Optic Neuropathy in Mice.Biomolecules · 2025Article
- The influence of soluble epoxide hydrolase inhibition and their PUFA-derived epoxides in osteoblast bone metabolism: an in vitro study.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- Effects of soluble epoxide hydrolase inhibition on liver injury and gut microbiota in mice chronically fed ethanol.Alcohol, clinical & experimental research · 2025Article
- Immunoregulatory mechanisms of the arachidonic acid pathway in cancer.FEBS letters · 2025Review
- Soluble epoxide hydrolase inhibition impairs triggering receptor expressed on myeloid cells-1 in periodontal tissue.Journal of periodontal research · 2025Article
- Inhibition of Soluble Epoxide Hydrolase Reduces Inflammation and Myocardial Injury in Arrhythmogenic Cardiomyopathy.JACC. Basic to translational science · 2025Article
- Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain.iScience · 2025Article
- Research on the mechanisms of plant bioactive metabolites in anti-skin aging and future development prospects.Frontiers in pharmacology · 2025Review
- Soluble epoxide hydrolase inhibition preserves alveolar bone in experimental periodontitis with estrogen deficiency.Frontiers in immunology · 2025Article
- The mechanisms of specialized pro-resolving mediators in pain relief: neuro-immune and neuroglial regulations.Frontiers in immunology · 2025Review
- The Involvement of Resolvins in Pathological Mechanisms of Periodontal Disease Associated with Type 2 Diabetes: A Narrative Review.International journal of molecular sciences · 2024Review
- Biosynthesis of resolvin D1, resolvin D2, and RCTR1 from 7,8(S,S)-epoxytetraene in human neutrophils and macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
background and purposeEpoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFA) are lipid mediators that are rapidly inactivated by soluble epoxide hydrolase (sEH). Uncontrolled and chronic inflammatory disorders fail to sufficiently activate endogenous regulatory pathways, including the production of specialized pro-resolving mediators (SPMs). Here, we addressed the relationship between SPMs and the EET/sEH axis and explored the effects of sEH inhibition on resolving macrophage phenotype. EXPERIMENTAL APPROACH: Mice were treated with a sEH inhibitor, EETs, or sEH inhibitor + EETs (combination) before ligature placement to induce experimental periodontitis. Using RT-qPCR, gingival samples were used to examine SPM receptors and osteolytic and inflammatory biomarkers. Maxillary alveolar bone loss was quantified by micro-CT and methylene blue staining. SPM levels were analysed by salivary metabolo-lipidomics. Gingival macrophage phenotype plasticity was determined by RT-qPCR and flow cytometry. Effects of sEH inhibition on macrophage polarization and SPM production were assessed with bone marrow-derived macrophages (BMDMs). KEY
resultsPharmacological inhibition of sEH suppressed bone resorption and the inflammatory cytokine storm in experimental periodontitis. Lipidomic analysis revealed that sEH inhibition augmented levels of LXA4, RvE1, RvE2, and 4-HDoHE, concomitant with up-regulation of LTB4R1, CMKLR1/ChemR23, and ALX/FPR2 SPM receptors. Notably, there is an impact on gingival macrophage plasticity was affected suggesting an inflammation resolving phenotype with sEH inhibition. In BMDMs, sEH inhibition reduced inflammatory macrophage activation, and resolving macrophages were triggered to produce SPMs. CONCLUSION AND IMPLICATIONS: Pharmacological sEH inhibition increased SPM synthesis associated with resolving macrophages, suggesting a potential target to control osteolytic inflammatory disorders.
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