Document Type : Original Article
Authors
1
Cancer Epidemiology Research Center (AJA-CERTC), AJA University of Medical Sciences, Tehran, Iran.
2
Toxicology Research Center, AJA University of Medical Sciences, Tehran, Iran.
3
School of Business, The Ingenuity Center, University of Nottingham, Nottingham, United Kingdom.
4
Faculty of Agriculture, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
5
Department of Genetics and Advanced Technologies, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.
6
Infectious Diseases Research Center, AJA University of Medical Sciences, Tehran, Iran. & Medical Biotechnology Research Center, AJA University of Medical Sciences, Tehran, Iran.
Abstract
Background: Excessive production of reactive oxygen species (ROS) is implicated in the pathogenesis of inflammatory and autoimmune disorders, partly through the dysregulation of T cell function. Curcumin and metformin possess well-documented antioxidant and anti-inflammatory properties, yet their combined effects on T cell oxidative stress have not been comprehensively evaluated.
Methods: Human peripheral blood T cells from healthy donors were treated with curcumin, metformin, or their combination. Intracellular ROS, superoxide, and glutathione (GSH) levels were quantified by flow cytometry. mRNA expression of key oxidative (NOX2) and antioxidant genes (CAT, SOD1, SOD2, NRF2) was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
Results: Both agents significantly decreased ROS levels and increased intracellular GSH compared with untreated cells. Metformin exhibited superior effects, reducing ROS by ~2.5-fold and increasing GSH nearly 3-fold compared to curcumin. Metformin also induced stronger upregulation of NRF2 and SOD2, and greater suppression of NOX2. Co-treatment produced no general synergistic effects on ROS, GSH, or most antioxidant genes, except for a significant synergistic increase in SOD1 expression.
Conclusion: Metformin outperformed curcumin in enhancing antioxidant defenses and suppressing ROS in T cells, whereas combined therapy showed limited interaction, confined to SOD1. These findings support metformin—alone or with curcumin—as a potential candidate for managing oxidative stress–driven immune disorders, warranting further in vivo and clinical evaluation.
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