Carnosine and advanced glycation end products: a systematic review
Advanced glycation end products (AGEs) are a cluster of heterogeneous molecules that are generated in a non-enzymatic reaction by the binding of sugars with amino groups of DNA, lipids and proteins. Carnosine is a naturally occurring dipeptide with antioxidant activity, which inhibits protein carbonylation and glycoxidation. This systematic review searched international sources for all published and unpublished original research in English from any year up to the end of April 2018. An electronic search of PubMed, Scopus and Google Scholar was conducted. 187 articles were initially found and 133 articles were selected after excluding duplicated data. Review articles, studies based on the components of carnosine and studies that were about the effects of carnosine on AGEs-induced changes were excluded. In total, 36 studies met the inclusion criteria. This included 19 in vitro studies, 15 animal studies and two human studies. All but two of the studies indicated that carnosine can prevent the formation of AGEs. The findings of this review indicating that carnosine has anti-glycating properties, and may hinder the formation of protein carbonyls and the cross-links induced by reduced sugars; however, there were few human studies. The mechanism by which carnosine prevents the formation of AGEs needs further investigation.
KeywordsAdvanced glycation end products Carnosine Carbonyls Methylglyoxal Pentosidine Carboxymethyl lysine
RG and SK conducted the search, and participated in manuscript writing. SK edited the manuscript. Both authors read and approved the final manuscript.
There is no source of financial support.
Compliance with ethical standards
Conflict of interest
The authors reported no conflict of interest.
Research involving human participants and/or animals
There were no human participants or animals.
Not applicable for this study.
- Abe H (2000) Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry (Mosc) 65:757–765Google Scholar
- Babizhayev MA (2012) Biomarkers and special features of oxidative stress in the anterior segment of the eye linked to lens cataract and the trabecular meshwork injury in primary open-angle glaucoma: challenges of dual combination therapy with N-acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed carnosine. Fundam Clin Pharmacol 26:86–117CrossRefPubMedGoogle Scholar
- Battah S, Ahmed N, Thornalley PJ (2002) Novel anti-glycation therapeutic agents: glyoxalase I mimetics. In: International congress series. Elsevier, Amsterdam, pp 107–111Google Scholar
- Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, Hong M, Luther T, Henle T, Kloting I, Morcos M, Hofmann M, Tritschler H, Weigle B, Kasper M, Smith M, Perry G, Schmidt AM, Stern DM, Haring HU, Schleicher E, Nawroth PP (2001) Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes 50:2792–2808CrossRefPubMedGoogle Scholar
- Gugliucci A, Smith M, Menini T (2002) Carnosine in physiological concentrations inhibits advanced glycation of histones by reactive trioses methylgyoxal and glyceraldehyde. Diabetes 51:A513Google Scholar
- Hipkiss AR, Michaelis J, Syrris P, Dreimanis M (1995b) Strategies for the extension of human life span. In: Perspectives in human biology: genes, ethnicity and ageing. World Scientific, Singapore, pp 59–70Google Scholar
- Houjeghani S, Kheirouri S, Faraji E, Jafarabadi MA (2018) l-Carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products, and tumor necrosis factor–α levels in patients with type 2 diabetes: a double-blind placebo-controlled randomized clinical trial. Nutr Res 49:96–106CrossRefPubMedGoogle Scholar
- Ito M, Shii D, Segami T, Kojima R, Suzuki Y (1992) Preventive actions of N-(3-aminopropionyl)-l-histidinato zinc (Z-103) through increases in the activities of oxygen-derived free radical scavenging enzymes in the gastric mucosa on ethanol-induced gastric mucosal damage in rats. Jpn J Pharmacol 59:267–274CrossRefPubMedGoogle Scholar
- Kheirouri S, Alizadeh M, Maleki V (2017) Zinc against advanced glycation end products. Clin Exp Pharmacol PhysiolGoogle Scholar
- Li JP, Gao Y, S-f Chu, Zhang Z, C-y Xia, Mou Z, X-y Song, W-b He, X-f Guo, N-h Chen (2014) Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol-and CCl 4-induced hepatic fibrosis. Acta Pharmacol Sin 35:1031CrossRefPubMedPubMedCentralGoogle Scholar
- Miller FP, Vandome AF, McBrewster J (2010) Glycolysis. Alphascript Publishing, Dortmund, GermanyGoogle Scholar
- Nakamura K, S-i Yamagishi, Adachi H, Kurita-Nakamura Y, Matsui T, Yoshida T, Imaizumi T (2007a) Serum levels of sRAGE, the soluble form of receptor for advanced glycation end products, are associated with inflammatory markers in patients with type 2 diabetes. Mol Med 13:185CrossRefPubMedPubMedCentralGoogle Scholar
- Nelson D, Cox M (2000) Lehninger principle of biochemistry, vol 16, 3rd edn. Worth publisher, New York, pp 567–597Google Scholar
- Orioli M, Vistoli G, Regazzoni L, Pedretti A, Lapolla A, Rossoni G, Canevotti R, Gamberoni L, Previtali M, Carini M (2011) Design, synthesis, ADME properties, and pharmacological activities of β-alanyl-d-histidine (d-carnosine) prodrugs with improved bioavailability. ChemMedChem 6:1269–1282CrossRefPubMedGoogle Scholar
- Rubtsov A, Schara M, Sentjurc M, Boldyrev A (1991) Hydroxyl radical-scavenging activity of carnosine: a spin trapping study. Acta Pharm Jugosl 41:401–407Google Scholar
- Wu H-C, Shiau C-Y, Chen H-M, Chiou T-K (2003) Antioxidant activities of carnosine, anserine, some free amino acids and their combination. J Food Drug Anal 11:148–153Google Scholar