Immunomodulatory effects of medicinal and edible plants in autoimmune diseases: mechanisms and therapeutic potential.

Autoimmune diseases (ADs) and related immune-mediated inflammatory disorders are characterized by loss of immune tolerance, persistent inflammatory activation, immune-cell imbalance, oxidative stress, and tissue-specific injury. Although conventional immunomodulatory therapies remain central to disease management, their long-term use may be limited by adverse effects, variable treatment responses, and high costs. Medicinal and edible plants (MEPs) provide a diverse source of bioactive compounds with potential immunoregulatory activity. This narrative review summarizes the immunological basis of representative autoimmune and immune-mediated inflammatory disorders and critically evaluates the mechanisms, therapeutic potential, and translational limitations of selected MEPs and their major active constituents. Current evidence indicates that MEP-derived interventions commonly regulate NF-κB, MAPK, JAK/STAT, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling, while also modulating imbalances in Th17/Treg and Th1/Th2 responses, oxidative stress, and tissue barrier dysfunction. In addition to these shared mechanisms, several disease-relevant regulatory patterns have emerged, including high mobility group box 1 (HMGB1) inhibition in lupus-associated renal injury, regulation of histone lactylation and ferroptosis in rheumatoid arthritis-associated synovial pathology, neutrophil modulation in inflammatory arthritis, and intestinal protection mediated by the microbiota-metabolite-aryl hydrocarbon receptor (AhR) axis in colitis. However, most available evidence is derived from cellular and animal studies, whereas high-quality clinical data remain limited. Poor bioavailability, variable chemical composition, insufficient formulation and dosage standardization, incomplete safety evaluation, and regulatory challenges continue to hinder clinical translation. MEPs therefore represent promising sources of adjunctive immunomodulatory strategies for ADs, but their therapeutic value requires further validation through standardized mechanistic studies and well-designed clinical trials.