Saffron and Immune Regulation: Influence on Inflammatory Biomarkers and Gene Expression in Rheumatoid Arthritis Publisher



Hadidi M ; Aryaeian N ; Mahmoudi M ; Abolghasemi J ; Hamidi Z ; Morvaridi M ; Akhlaghi M
Source: Journal of Herbal Medicine Published:2025

Abstract

Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by persistent joint inflammation and progressive damage, largely mediated by pro-inflammatory cytokines. Saffron (Crocus sativus), a medicinal plant rich in bioactive compounds, has shown anti-inflammatory and immunomodulatory properties in preclinical studies. This trial aimed to evaluate the effects of saffron supplementation on inflammatory markers and immune-related gene expression in patients with active RA. Methods In this randomised, double-blind, placebo-controlled trial, 72 adult patients aged 18–65 years with active RA were assigned to receive either 100 mg/d of saffron powder (n = 36) or a matched placebo (n = 36) for 12 weeks. Clinical assessments, cytokine measurements (IL-17, IL-4), and quantitative gene expression analyses (FoxP3, RORγt, NF-κB, T-bet) were conducted at baseline and post-intervention. Results Saffron supplementation significantly reduced Patient Global Assessment (PGA) scores (P < 0.001) and IL-17 levels (P = 0.002) compared to placebo, while IL-4 levels remained unchanged (P = 0.610). Gene expression analysis revealed a significant upregulation of FoxP3 and downregulation of RORγt, NF-κB, and T-bet in the saffron group (P < 0.05). Conclusion Saffron supplementation may offer therapeutic benefits in RA by modulating key inflammatory pathways and enhancing regulatory immune responses. These findings support the potential of saffron as a complementary approach in RA management. Further studies are warranted to validate these results and elucidate underlying mechanisms. Trial registration IRCT, IRCT201707309472N15. Registered October 15, 2017, https://irct.behdasht.gov.ir/trial/10062 . © 2025 Elsevier B.V., All rights reserved.