Quinic and Ferulic Acid-Loaded Chitosan Nanoparticles Attenuate Experimental Ulcerative Colitis by Modulating the IL-32/IL-33/IL-34 Axis and NF-κB Signaling.

Abstract

Introduction: Ulcerative colitis (UC) is characterized by immune dysregulation and localized inflammation of the colonic mucosa. Despite advances in therapy, effective treatment remains difficult. This study aimed to investigate the immunomodulatory and therapeutic effects of chitosan nanoparticles (CS-NPs) loaded with quinic acid (QA) and ferulic acid (FA) in an experimental model of UC, focusing on the IL-32/IL-33/IL-34 cytokine axis and the NF-κB signaling pathway.

Methods: Eighty male Wistar rats were randomly divided into 10 groups (n = 8 per group). Experimental acute colitis was induced in rats via intrarectal administration of 4% acetic acid (AA). After induction, the animals received CS-NPs loaded with QA and FA for seven consecutive days. IL-33, IL-34, and NF-κB mRNA expression were measured by real-time PCR. Additionally, tissue IL-32 levels were measured using an ELISA kit.

Results: Induction of UC significantly increased IL-32 protein levels as well as the expression of IL-33, IL-34, and NF-κB. Oral administration with mesalazine, FA/QA/CS-NPs, QA/CS-NPs, FA/CS-NPs, FA/QA, QA, and FA significantly decreased IL-32 protein levels and the expression of IL-33, IL-34, and NF-κB relative to the model group.

Conclusion: FA/QA-loaded CS-NPs exhibit anti-inflammatory effects in experimental UC, likely through modulation of the IL-32/IL-33/IL-34 cytokine axis and NF-κB signaling. These findings suggest that FA/QA/CS-NPs may serve as a promising herbal-based therapeutic candidate for the treatment of UC in humans.