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Antioxidants
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Carnosine: A Multifaceted Antioxidant and Anti-Inflammatory Peptide—Molecular Mechanisms and Biological...
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Carnosine: A Multifaceted Antioxidant and Anti-Inflammatory Peptide—Molecular Mechanisms and Biological Relevance

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Natural and Synthetic Antioxidants".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 1262

Special Issue Editor

Prof. Dr. Giancarlo Aldini

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milan, Italy
Interests: reactive carbonyls species; advanced glycation end products (AGEs); advanced lipoxidation end products (ALEs); sequestering agents; protein adducts
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide with well-documented antioxidant and anti-inflammatory properties that are increasingly relevant in the context of chronic and degenerative diseases. Although a large body of experimental evidence supports its cytoprotective activity, the molecular mechanisms underlying these effects remain incompletely resolved.

Early studies primarily attributed carnosine’s biological actions to its direct scavenging of reactive oxygen species and reactive carbonyl species. However, accumulating evidence indicates that carnosine also modulates redox-sensitive signaling pathways, including Nrf2-dependent responses, suggesting a broader mechanism of action that extends beyond simple chemical antioxidant activity. This paradigm shift raises critical questions regarding the contribution of carnosine metabolites, adduct formation with electrophilic species and downstream effects on cellular stress adaptation and inflammation.

Given the central role of oxidative and carbonyl stress in aging, metabolic disorders, neurodegeneration and cancer, a deeper mechanistic understanding of carnosine biology is urgently needed. Clarifying how carnosine integrates chemical scavenging with redox signaling may unlock new therapeutic perspectives.

This Special Issue welcomes original research and critical reviews addressing the molecular mechanisms, disease relevance and translational potential of carnosine in oxidative stress and inflammation-related pathologies.

Prof. Dr. Giancarlo Aldini
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • carnosine
  • reactive carbonyl species scavenging
  • anti-inflammatory dipeptides
  • oxidative stress pathologies
  • carbonyl stress protection

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Published Papers (1 paper)

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Research

27 pages, 5831 KB  
Article
The Carnosine–HNE Michael Adduct as a Redox-Active Species Associated with Nrf2-Dependent Antioxidant and Anti-Inflammatory Responses
by Alessandra Altomare, Giovanna Baron, Francesca Gado, Larissa Della Vedova, Giulio Ferrario, Lara Davani, Ettore Gilardoni, Rebecca Ferrisi, Clara Mocchetti, Lavpreet Singh, Barbora De Courten, Marina Carini, Rosalba Siracusa, Ramona D’Amico, Rosanna Di Paola, Clelia Dallanoce, Daniela Impellizzeri and Giancarlo Aldini
Antioxidants 2026, 15(3), 388; https://doi.org/10.3390/antiox15030388 - 19 Mar 2026
Viewed by 864
Abstract
Carnosine (CAR), an endogenous histidine-containing dipeptide, exhibits antioxidant and anti-inflammatory activity in various experimental models; however, its molecular mechanism of action remains poorly understood. Here, we demonstrate that the Michael adduct between CAR and 4-hydroxy-2-nonenal (HNE), which has been detected in previous studies [...] Read more.
Carnosine (CAR), an endogenous histidine-containing dipeptide, exhibits antioxidant and anti-inflammatory activity in various experimental models; however, its molecular mechanism of action remains poorly understood. Here, we demonstrate that the Michael adduct between CAR and 4-hydroxy-2-nonenal (HNE), which has been detected in previous studies in both in vitro and in vivo settings, mediates its bioactivity, particularly its antioxidant and anti-inflammatory responses, through Nrf2 activation. The CAR–HNE adduct was synthesized and its physicochemical, metabolic, and biological properties were evaluated. CAR–HNE exhibited high stability in biological matrices and retained the ability to transfer HNE to thiol nucleophiles at a slow rate under physiologically relevant conditions, consistent with electrophile-mediated Nrf2 activation. This kinetic behavior limits the cytotoxicity typically associated with free HNE while preserving the redox signaling capacity. CAR–HNE induced dose-dependent Nrf2 activation and NF-κB inhibition in cell-based assays without the hormetic toxicity observed for free HNE. Mechanistically, CAR–HNE may act as a redox-tunable electrophilic reservoir, restoring nucleophilic tone and modulating redox-sensitive transcription factors. In vivo, CAR–HNE attenuated DSS-induced colitis more effectively than equimolar doses of either carnosine or HNE alone. Proteomic analyses revealed modulation of canonical Nrf2-dependent antioxidant pathways. Our findings suggest a conceptual shift in carnosine biology: rather than acting as a classical antioxidant or carbonyl quencher, carnosine functions as a precursor of redox-active electrophilic adducts that transduce anti-inflammatory and antioxidant responses via controlled RCS signaling. Full article
(This article belongs to the Special Issue Carnosine: A Multifaceted Antioxidant and Anti-Inflammatory Peptide—Molecular Mechanisms and Biological Relevance)
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