Chicoric acid in autoimmunity: A review of its immunomodulatory mechanisms and therapeutic potential.

Abstract

Autoimmune diseases are characterized by the breakdown of immune self-tolerance, leading to aberrant immune attacks against self-antigens and resulting in persistent systemic inflammation and multi-organ damage. Despite decades of advances in glucocorticoid, immunosuppressant, and biologic therapies, the clinical management of ADs remains challenged by unsatisfactory long-term efficacy, high rates of severe adverse events, and limited patient accessibility. Chicoric acid (CA), a naturally occurring phenolic compound renowned for its potent anti-inflammatory, antioxidant, and immunomodulatory activities, has recently garnered attention as a promising therapeutic candidate for ADs. In this review, we systematically summarize the natural sources, synthetic pathways, and chemical structure of CA, with a particular emphasis on its regulatory mechanisms in adaptive and innate immunity. We further discuss its therapeutic effects and underlying signaling pathways in representative ADs, including ulcerative colitis and rheumatoid arthritis, and extend the discussion to its potential applications in other autoimmune conditions, including systemic lupus erythematosus, multiple sclerosis, and myasthenia gravis. Collectively, this review establishes a theoretical foundation for the preclinical research of CA, highlights its translational potential as a novel natural immunomodulator for the management of ADs, and offers insights for future drug development and rational clinical application of this compound.