ArticleRedox biology2020
Therapeutic effects of CO-releaser/Nrf2 activator hybrids (HYCOs) in the treatment of skin wound, psoriasis and multiple sclerosis.
Article in Redox biology, 2020. 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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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Oral Delivery Systems for Gasotransmitters in Therapeutic Applications.Polymer science & technology (Washington, D.C.) · 2026Review
- Activation of Nrf2 with natural flavonoids and mesenchymal stromal/stem cells: mechanisms and therapeutic potential for inflammatory diseases.Stem cell research & therapy · 2026Review
- Emerging Therapeutic Strategies for Nrf2-Associated Skin Disorders: From Photoaging to Autoimmunity.Antioxidants (Basel, Switzerland) · 2026Review
- Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis.Nature communications · 2025Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- A Highly Potent Apomorphine Derivative Enhancing Neurite Outgrowth via Nrf2 Activation.Antioxidants (Basel, Switzerland) · 2025Article
- Immunomodulatory effects of HYCO-3, a dual action CO-releaser/Nrf2 activator.Clinical and experimental immunology · 2025Article
- Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.Current drug targets · 2025Review
- The untapped potential of targeting NRF2 in neurodegenerative disease.Frontiers in aging · 2023Article
- An organometallic analogue of combretastatin A-4 and its apoptosis-inducing effects on lymphoma, leukemia and other tumor cellsRSC medicinal chemistry · 2022Article
- Recent advances on endogenous gasotransmitters in inflammatory dermatological disorders.Journal of advanced research · 2022Review
- Heme-oxygenase and lipid mediators in obesity and associated cardiometabolic diseases: Therapeutic implications.Pharmacology & therapeutics · 2022Review
- Carbon Monoxide-Neuroglobin Axis Targeting Metabolism Against Inflammation in BV-2 Microglial Cells.Molecular neurobiology · 2022Article
- A Journey into the Clinical Relevance of Heme Oxygenase 1 for Human Inflammatory Disease and Viral Clearance: Why Does It Matter on the COVID-19 Scene?Antioxidants (Basel, Switzerland) · 2022Review
- Article
- "CO in a pill": Towards oral delivery of carbon monoxide for therapeutic applications.Journal of controlled release : official journal of the Controlled Release Society · 2021Review
- Article
- Redox regulation of immunity and the role of small molecular weight thiols.Redox biology · 2021Article
- Regulation of inflammation by the antioxidant haem oxygenase 1.Nature reviews. Immunology · 2021Review
- Targeting Heme Oxygenase-1 in the Arterial Response to Injury and Disease.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Carbon monoxide (CO) produced by heme oxygenase-1 (HO-1) or delivered by CO-releasing molecules (CO-RMs) exerts anti-inflammatory action, a feature also exhibited by the nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the stress response. We have recently developed new hybrid molecules (HYCOs) consisting of CO-RMs conjugated to fumaric esters known to activate Nrf2/HO-1. Here we evaluated the biological activities of manganese (Mn) and ruthenium (Ru)-based HYCOs in human monocytes and keratinocytes in vitro as well as in vivo models of inflammation. The effects of HYCOs were compared to: a) dimethyl fumarate (DMF), a known fumaric ester used in the clinic; b) a CO-RM alone; or c) the combination of the two compounds. Mn-HYCOs donated CO and up-regulated Nrf2/HO-1 in vitro more efficiently than Ru-HYCOs. However, irrespective of the metal, a strong reduction in anti-inflammatory markers in monocytes stimulated by LPS was observed with specific HYCOs. This effect was not observed with DMF, CO-RM alone or the combination of the two, indicating the enhanced potency of HYCOs compared to the separate entities. Selected HYCOs given orally to mice accelerated skin wound closure, reduced psoriasis-mediated inflammation and disease symptoms equalling or surpassing the effect of DMF, and ameliorated motor dysfunction in a mouse model of multiple sclerosis. Thus, HYCOs have potent anti-inflammatory activities that are recapitulated in disease models in which inflammation is a prominent component. Prolonged daily administration of HYCOs (up to 40 days) is well tolerated in animals. Our results clearly confirm that HYCOs possess a dual mode of action highlighting the notion that simultaneous Nrf2 targeting and CO delivery could be a clinically relevant application to combat inflammation.
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