Anti-Inflammatory Effects of Urocanic Acid Derivatives in Models Ex Vivo and In Vivo of Inflammatory Bowel Disease

Abstract

Urocanic acid (UCA) derivatives were tested for their anti-inflammatory activity in inflammatory bowel disease (IBD) in two models: ex vivo and an experimental mouse model. Ex vivo: inflamed colonic tissue was incubated in culture medium with or without the UCA derivatives. Biopsies, incubated with UCA derivatives, produced lower levels of proinflammatory cytokines IL-6 and IL-8 as compared to control biopsies. The same compounds also showed increased levels of IL-10, providing an additional indication for anti-inflammatory properties. In vivo: a combination of two imidazoles and a combination of two of their ethyl esters were administered to mice while colitis was induced by oral administration of dextran sodium sulfate (DSS). Some parameters did not show conclusive effects, but the imidazoles and their ethyl esters reduced the area of inflammation and the number of infiltrating neutrophils. Fibrosis and the sum of all histological aspects were reduced by the imidazoles, whereas the ethyl esters reduced the colon weight to length ratio. These results suggest that the UCA derivatives have anti-inflammatory effect on IBD. In addition, fine tuning of the ex vivo model may provide an elegant way to predict anti-inflammatory effects of potential drugs in humans, which may decrease the need for animal experiments.

Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis

“…Urocanic acid is one metabolite which is involved histidine metabolism. The results of a recent study showed urocanic acid derivatives have anti-inflammatory effects on inflammatory bowel disease [34], supporting the decreased levels of urocanic acid in our AOSD patients. Indole, another important metabolite, is a product of amino acid (tryptophan) metabolism.…”

Sanitary Conditions on the Farm Alters Fecal Metabolite Profile in Growing Pigs

“…Like other branched SCFAs, valerate has been shown to modulate innate immune responses via specific receptors on macrophages and T cells [12,13]. In this and the previous study [3], we observed a higher content of urocanic acid (i.e., Bin number 7.86; uridine derivatives), which is known for its antiinflammatory activity [14]. Such immune-related metabolites, such as valerate and urocanic acid, are produced in the gut as a result of a local immune response that regulates host gut health.…”

The gut‐skin axis in health and disease: A paradigm with therapeutic implications

“…Irradiation of the skin with ultraviolet B induces expression of the β‐endorphins which have analgesic and pigmentary effects . Synthesis of vitamin D (low in IBD, ) and urocanic acid which has been shown to suppress inflammation in models of IBD, also occurs in response to irradiation of the skin . Thus, selective manipulation of the skin by topically applied agents or UV‐irradiation, with its often underappreciated secretory and metabolic capacity, may offer new adjunctive therapies in GI diseases.…”