Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice

Autoimmune disease is highly prevalent in humans. Since conventional therapies have limited efficacy and often come with significant side effects, nutrition may provide an alternative and complementary approach to improving autoimmune disorders. Naringenin, a flavonoid found in citrus fruits, has been shown to have anti-inflammatory and antioxidant properties. Using the experimental autoimmune encephalomyelitis (EAE), a rodent model of human multiple sclerosis, we determined the effect of dietary naringenin (0.5%) on autoimmune disease. We found that naringenin reduced the incidence, delayed the onset, and attenuated the symptoms of EAE, which were accompanied by reduced immune cell infiltration and demyelination in the spinal cord. Additionally, the pro-inflammatory CD4+ T cell subsets Th1, Th9, and Th17 cells together with their respective transcription factors T-bet, PU.1, and RORγt were reduced in both the central nervous system (CNS) and lymph nodes of EAE mice fed naringenin while no difference was found in Th2 and regulatory T cell (Treg) populations in either CNS or lymph nodes between the two groups. We further showed that pathologic T cell proliferation induced by ex vivo re-stimulation with MOG35-55 and proinflammatory cytokines IL-6 and TNF-α were lower in naringenin-fed mice than in the control mice. Additionally, we found that naringenin treatment inhibited mRNA expression of CXCL10 (Th1 recruiting chemokine), vascular cell adhesion molecule-1 (VCAM-1), and VLA-4 (VCAM-1 ligand) in the CNS of EAE mice. Altogether, these results indicate that naringenin may have a potential to ameliorate autoimmune disease by favorably modulating autoimmune response.