ArticleMetabolites2021
Ultramicronized Palmitoylethanolamide Inhibits NLRP3 Inflammasome Expression and Pro-Inflammatory Response Activated by SARS-CoV-2 Spike Protein in Cultured Murine Alveolar Macrophages.
Article in Metabolites, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Trial
- A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain.Inflammopharmacology · 2022Trial
- Palmitoylethanolamide Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial.The Journal of nutrition · 2022Trial
- An olive oil-derived NAE mixture (OlaliamidBMC veterinary research · 2025Article
- Palmitoylethanolamide: A Multifunctional Molecule for Neuroprotection, Chronic Pain, and Immune Modulation.Biomedicines · 2025Article
- Article
- Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling.Cells · 2024Article
- Ultramicronized Palmitoylethanolamide and Luteolin: Drug Candidates in Post-COVID-19 Critical Illness Neuropathy and Positioning-Related Peripheral Nerve Injury of the Upper Extremity.Journal of hand and microsurgery · 2024Article
- Carbon dioxide and MAPK signalling: towards therapy for inflammation.Cell communication and signaling : CCS · 2023Review
- Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology.Frontiers in immunology · 2023Review
- The role of peroxisome proliferator-activated receptors in the modulation of hyperinflammation induced by SARS-CoV-2 infection: A perspective for COVID-19 therapy.Frontiers in immunology · 2023Review
- First Evidence of the Protective Effects of 2-Pentadecyl-2-Oxazoline (PEA-OXA) in In Vitro Models of Acute Lung Injury.Biomolecules · 2022Article
- A comparative study of spike protein of SARS-CoV-2 and its variant Omicron (B.1.1.529) on some immune characteristics.Scientific reports · 2022Article
- N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism.Biomolecules · 2022Article
- Palmitoylethanolamide (PEA) Inhibits SARS-CoV-2 Entry by Interacting with S Protein and ACE-2 Receptor.Viruses · 2022Article
- PPAR Ligands Induce Antiviral Effects Targeting Perturbed Lipid Metabolism during SARS-CoV-2, HCV, and HCMV Infection.Biology · 2022Review
- Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization.Open life sciences · 2022Article
- Blood gene expression predicts intensive care unit admission in hospitalised patients with COVID-19.Frontiers in immunology · 2022Article
- Therapeutic Targeting of Innate Immune Receptors Against SARS-CoV-2 Infection.Frontiers in pharmacology · 2022Review
- Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2 cell line.Phytotherapy research : PTR · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite its possible therapeutic potential against COVID-19, the exact mechanism(s) by which palmitoylethanolamide (PEA) exerts its beneficial activity is still unclear. PEA has demonstrated analgesic, anti-allergic, and anti-inflammatory activities. Most of the anti-inflammatory properties of PEA arise from its ability to antagonize nuclear factor-κB (NF-κB) signalling pathway via the selective activation of the PPARα receptors. Acting at this site, PEA can downstream several genes involved in the inflammatory response, including cytokines (TNF-α, Il-1β) and other signal mediators, such as inducible nitric oxide synthase (iNOS) and COX2. To shed light on this, we tested the anti-inflammatory and immunomodulatory activity of ultramicronized(um)-PEA, both alone and in the presence of specific peroxisome proliferator-activated receptor alpha (PPAR-α) antagonist MK886, in primary cultures of murine alveolar macrophages exposed to SARS-CoV-2 spike glycoprotein (SP). SP challenge caused a significant concentration-dependent increase in proinflammatory markers (TLR4, p-p38 MAPK, NF-κB) paralleled to a marked upregulation of inflammasome-dependent inflammatory pathways (NLRP3, Caspase-1) with IL-6, IL-1β, TNF-α over-release, compared to vehicle group. We also observed a significant concentration-dependent increase in angiotensin-converting enzyme-2 (ACE-2) following SP challenge. um-PEA concentration-dependently reduced all the analyzed proinflammatory markers fostering a parallel downregulation of ACE-2. Our data show for the first time that um-PEA, via PPAR-α, markedly inhibits the SP induced NLRP3 signalling pathway outlining a novel mechanism of action of this lipid against COVID-19.
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Registered trials
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.