Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Crocin as an immunomodulator: Cytokine signatures and oxidative-inflammatory crosstalk

Articles in Press

Document Type : Review Article

Authors
Hakimeh Abdi 1, 2
Zahra Aganj 3
Fatemeh Valinezhad Sani 4
Hossein Hosseinzadeh 5
Fatemeh Kalalinia 6, 7
Fatemeh Mosaffa 6, 7
1 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
2 Department of Pharmaceutics, School of Pharmacy, Babol University of Medical Sciences, Babol, Iran
3 Student Research Committee, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
4 4 Department of Laboratory Sciences, Faculty of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
5 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
6 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
7 Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/ijbms.2026.93565.20185
Abstract
mmune dysregulation triggers numerous pathologies, including chronic inflammation, autoimmunity, and immunodeficiency. Immunomodulators return immune balance by suppressing, stimulating, or reprogramming immune responses. Crocin, a bioactive carotenoid from Crocus sativus L. (saffron), exhibits broad immunomodulatory, anti-inflammatory, and antioxidant properties, offering a potential alternative to synthetic immunomodulators with adverse side effects. This review synthesizes evidence on crocin’s immunomodulatory effects, primarily from experimental models, focusing on its impact on inflammatory mediators, cytokines, and immune cell activity. A literature search was conducted in the Web of Science and PubMed databases from 2001 to 2026 to identify studies evaluating crocin’s effects on immune markers in vitro (using immune cells and tissues) and in vivo (in human and animal models). Analyzed biomarkers included cytokines (e.g., TNF-α, IL-6, IL-10), enzymes (e.g., iNOS, COX-2), oxidative stress markers (e.g., MDA, ROS), and signaling pathways (e.g., NF-κB, TLRs). Crocin modulates macrophage polarization, suppresses neutrophil infiltration, and regulates lymphocyte proliferation. It enhances dendritic cell maturation and mesenchymal stem cell anti-inflammatory cytokine secretion. Crocin reduces pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in serum, brain, liver, lung, kidney, and joints. It attenuates oxidative stress and the NF-κB activation systemically. Crocin demonstrates pleiotropic immunomodulatory effects across diverse pathologies, supporting its therapeutic potential for immune-related disorders. Further clinical studies are warranted to validate its efficacy and safety in humans.
Keywords
Crocin
Cytokines
Immunomodulation
Inflammation
Oxidative stress
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 31 August 2026