ArticleMolecular medicine (Cambridge, Mass.)2015
Aspirin's Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses.
Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 119 citations in OpenAlex.
- Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial.Inflammopharmacology · 2022Trial
- High mobility group motif proteins' role in fibrosis, inflammation, and vascular injury in systemic sclerosis.Journal of molecular medicine (Berlin, Germany) · 2026Review
- HMGB1-Platelet Interactions: Mechanisms and Targeted Therapy Strategies.Thrombosis and haemostasis · 2026Review
- Engineering controlled-release steroid therapeutics: fabrication and molecular design of self-assembled microparticles.Science advances · 2026Article
- HMGB1: A New Target for Ischemic Stroke and Hemorrhagic Transformation.Translational stroke research · 2025Review
- Advanced Research in the Pathophysiology of Venous Thromboembolism-Acute Pulmonary Embolism.Biomedicines · 2025Review
- Pathophysiological role of high mobility group box-1 signaling in neurodegenerative diseases.Inflammopharmacology · 2025Review
- Targeting high-mobility-group-box-1-mediated inflammation: a promising therapeutic approach for myocardial infarction.Inflammopharmacology · 2025Review
- A potent nonapeptide inhibitor for the CXCL12/HMGB1 heterocomplex: A computational and experimental approach.Computational and structural biotechnology journal · 2025Article
- High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies.Cells · 2024Review
- Simultaneous Qualitative and Quantitative Analyses of 41 Constituents inMolecules (Basel, Switzerland) · 2024Article
- Ligands of HMG-like dorsal switch protein 1 ofHeliyon · 2024Article
- Flavonoids Regulate Redox-Responsive Transcription Factors in Glioblastoma and Microglia.Cells · 2023Article
- Role of Metabolism and Metabolic Pathways in Prostate Cancer.Metabolites · 2023Review
- Shared and Related Molecular Targets and Actions of Salicylic Acid in Plants and Humans.Cells · 2023Review
- On the human health benefits of microalgal phytohormones: An explorativeComputational and structural biotechnology journal · 2023Article
- HMGB1: a double-edged sword and therapeutic target in the female reproductive system.Frontiers in immunology · 2023Review
- Pamoic acid is an inhibitor of HMGB1·CXCL12 elicited chemotaxis and reduces inflammation in murine models of Pseudomonas aeruginosa pneumonia.Molecular medicine (Cambridge, Mass.) · 2022Article
- Changing Perspectives from Oxidative Stress to Redox Signaling-Extracellular Redox Control in Translational Medicine.Antioxidants (Basel, Switzerland) · 2022Review
- Low-dose aspirin protects unexplained recurrent spontaneous abortionFrontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
Salicylic acid (SA) and its derivatives have been used for millennia to reduce pain, fever and inflammation. In addition, prophylactic use of acetylsalicylic acid, commonly known as aspirin, reduces the risk of heart attack, stroke and certain cancers. Because aspirin is rapidly de-acetylated by esterases in human plasma, much of aspirin's bioactivity can be attributed to its primary metabolite, SA. Here we demonstrate that human high mobility group box 1 (HMGB1) is a novel SA-binding protein. SA-binding sites on HMGB1 were identified in the HMG-box domains by nuclear magnetic resonance (NMR) spectroscopic studies and confirmed by mutational analysis. Extracellular HMGB1 is a damage-associated molecular pattern molecule (DAMP), with multiple redox states. SA suppresses both the chemoattractant activity of fully reduced HMGB1 and the increased expression of proinflammatory cytokine genes and cyclooxygenase 2 (COX-2) induced by disulfide HMGB1. Natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 were identified, providing proof-of-concept that new molecules with high efficacy against sterile inflammation are attainable. An HMGB1 protein mutated in one of the SA-binding sites identified by NMR chemical shift perturbation studies retained chemoattractant activity, but lost binding of and inhibition by SA and its derivatives, thereby firmly establishing that SA binding to HMGB1 directly suppresses its proinflammatory activities. Identification of HMGB1 as a pharmacological target of SA/aspirin provides new insights into the mechanisms of action of one of the world's longest and most used natural and synthetic drugs. It may also provide an explanation for the protective effects of low-dose aspirin usage.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.