Urocanic acid

The Multiple Roles of Urocanic Acid in Health and Disease

Trans-urocanic acid (trans-UCA) is synthesized in the skin, liver, and brain. It is a major natural moisturizing factor in skin and maintains its acid pH. In skin, it isomerizes to cis-UCA following exposure to UVR. Both isomers fulfill multiple roles in health and disease. Cis-UCA has immunomodulatory properties linked with several cutaneous diseases such as skin cancer, atopic dermatitis, and urticaria and associates with systemic diseases including multiple sclerosis. The levels of UCA in the skin, brain, urine, and feces reflect some physiological processes and may be disease biomarkers. Both isomers of UCA have therapeutic potential for a range of disorders.

Urocanic acid and immunosuppression

Urocanic acid, a molecule found at high concentration in the stratum corneum, acts as a photoreceptor for UV-light, isomerizing from the naturally occurring trans-form to the cis-form. It has been proposed that cis-urocanic acid may mediate the transient alteration in immune surveillance resulting in immunosuppression induced after UV-irradiation, by interacting with immune cells locally and/or systemically to generate T cells with suppressor function. The evidence to support this hypothesis is summarized, and possible interactions of urocanic acid with immune cells and their outcome are discussed.

Analytical tools for urocanic acid determination in human samples: A review

Urocanic acid is a chromophore found in the skin that has been identified as an important immunosuppressant and carcinogenesis mediator through its photoisomerization from trans to cis form induced by ultraviolet radiation. Research on analytical methods that explore urocanic acid isomerization is indispensable to fully understand the deleterious effects mediated by this biomarker. In this context, the current relevant analytical methods for determination of these isomers in human samples are summarized in this review. The methods presented here are applicable to human samples collected by noninvasive methods (or minimally invasive), encompassing an array of analytical techniques, including high-performance capillary electrophoresis, confocal Raman spectroscopy, gas chromatography, high-performance liquid chromatography, and mass spectrometry, among others. Developed high-performance liquid chromatography methods have proven to be advantageous, allowing noninvasive collections for in vivo analysis and the confocal Raman, specially, for real-time analysis. Among all these methods, high-performance liquid chromatography is the most investigated one with mass spectrometry or ultraviolet detector, and the mass spectrometry detector being the most studied in the last years, demonstrating high sensitivity, very low detection limits, and accurate identification, especially for clinical investigations.

Trans-urocanic acid facilitates spatial memory, implications for Alzheimer's disease

Trans-urocanic acid (trans-UCA) is an isomer of cis-UCA and is widely distributed in the brain, predominantly in the hippocampus and prefrontal cortex. Previous studies have investigated the role of trans-UCA in non-spatial memory; however, its influence on spatial memory remains unclear. In the present study, network pharmacology strategy and behavioral testing were used to evaluate the role of trans-UCA in spatial memory and predict its possible mechanism. The results showed that there are 40 intersecting targets between trans-UCA and spatial memory identified by several databases and Venn diagram, indicating that trans-UCA may be involved in spatial memory. Behavioral results show that trans-UCA facilitates spatial working memory in the Y-maze test as well as spatial recognition memory acquisition, consolidation and retrieval in an object location recognition (OLR) task. Furthermore, PPI (protein-protein interaction) network analysis, GO (gene ontology) and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses show that the molecular mechanisms underlying the enhancing effect of trans-UCA on spatial memory are mainly associated with the regulation of insulin, mitogen-activated protein kinase (MAPK) and nuclear factor Kappa B (NF-κB) signaling pathways, serotonergic synapse and arginine and proline metabolism. The results of this study suggest that trans-UCA facilitates spatial memory in the Y-maze test and OLR task and may offer therapeutic potential for Alzheimer's disease (AD). The underlying mechanisms predicted by network pharmacology should be further verified.

High pressure Raman investigation on trans-urocanic acid

Trans-urocanic acid (t-UCA) is an important epidermal UV protector predominantly found in human skin. Exposure of UV radiation triggers photoisomerization of t-UCA into its other conformer, cis-urocanic acid (cis-UCA), which has been shown to be a mediator of UV-induced immune-suppression leading to skin cancer. In this report, we present the investigation of molecular changes of t-UCA under high pressures by in-situ high pressure Raman spectroscopy. The study indicates onset of ring opening polymerization of t-UCA at pressure above 1.4 GPa. At pressures beyond 5 GPa, a well discernible characteristic vibrational mode (CC stretch) accompanied by several other spectral features such as δ CO₂^- and δ NH modes of cis-UCA point towards the isomerization of residual t-UCA monomers into cis-UCA. The content of cis-UCA gradually increased with increase in pressure. On release to ambient conditions, the spectrum of the quenched sample showed Raman modes of polymer and cis-UCA indicating that the changes are irreversible.