Phytocompounds with immunomodulatory activities: mechanisms, therapeutic potential, and clinical prospects

The immune system is essential for host defense, immune surveillance, and maintenance of physiological homeostasis; its dysregulation underlies a broad spectrum of disorders, including autoimmune, inflammatory, infectious, neoplastic, and immunodeficiency diseases. Despite advances in modern immunotherapy, current treatments remain limited by suboptimal efficacy, adverse effects, resistance, and high cost, necessitating the development of safer and more effective immunomodulatory strategies. This review provides a comprehensive and integrative synthesis of phytocompounds as emerging immunomodulators, with emphasis on their mechanisms and translational potential. A structured literature search was conducted using major databases (PubMed, Scopus, and Web of Science) covering studies published between 2000 and 2025. We systematically analyze major classes of bioactive phytocompounds, including polysaccharides, flavonoids, polyphenols, terpenoids, and alkaloids, highlighting their capacity to modulate both innate and adaptive immune responses. These compounds exert pleiotropic effects through regulation of key immune cells; macrophages, dendritic cells, T and B lymphocytes, and natural killer cells, and modulation of critical signaling pathways such as NF-κB, MAPKs, JAK/STAT, and Nrf2. Importantly, this review bridges preclinical findings with clinical evidence, critically evaluating their therapeutic potential in autoimmune diseases, chronic inflammatory conditions, infections, and immune-mediated metabolic disorders. Despite promising outcomes, challenges related to safety and clinical validation remain. Future research should focus on pharmacokinetics, standardized dosing, and large-scale clinical trials to support their therapeutic translation.