Insights in pharmacological activities and the gastrointestinal stability of paraconic acids from Cetraria islandica (L.) Ach

Ethnopharmacological relevance: Cetraria islandica, often used for the treatment of respiratory diseases, is also described as remedy to treat gastric and duodenal ulcers. Among the known constituents, paraconic acids, such as lichesterinic and protolichesterinic acid, have shown several pharmacological activities, including inhibition of 5-LOX and COX isoenzymes. Interestingly, they can be extracted into hot water preparations, but their possible contribution to activities in the gastrointestinal tract remains unknown. Aim of the study: To identify the activity contribution of paraconic acids in the treatment of intestinal complaints. Methods: Isolated paraconic acids were extensively evaluated in vitro to understand their biological effects on intestinal epithelial cells (IEC-6) after LPS-IFN-γ stimulation. The study focused on their ability to modulate key cellular responses, specifically evaluating levels of intracellular Reactive Oxygen Species (ROS), as well as the antioxidant enzymes NQO1 and SOD-2. Furthermore, their impact on E-cadherin expression and wound healing capabilities were investigated under the same experimental conditions. In a second step, biological relevance was evaluated by stability monitoring in a gastrointestinal digestion model with colon phase. Results: Outcomes of the performed experiments indicate that paraconic acids exert antioxidant activity and promote wound healing in intestinal epithelial cells during LPS-IFN-γ stimulation. Analysis of the metabolic fate of paraconic acids after oral administration using an in vitro digestion model, including the colon phase, revealed an unexpected stability of this class of natural compounds throughout the whole experiment, emphasizing their contribution to the pharmacological activities. Conclusion: Paraconic acids showed in vitro antioxidant and wound healing effects in IEC-6, combined with an unexpected chemical stability during digestion. Together with known anti-inflammatory properties, paraconic acids represent an interesting compound class for the treatment of intestinal inflammatory diseases, and might explain the traditional use of C. islandica for gastro-intestinal indications.