|WANG, JUNPENG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|QI, YING - Tianjin University|
|NIU, XINLI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|TANG, HUA - Tianjin University|
|MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2017
Publication Date: 4/1/2018
Citation: Wang, J., Qi, Y., Niu, X., Tang, H., Meydani, S.N., Wu, D. 2018. Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice. Journal of Nutritional Biochemistry. 54:130-139. https://doi.org/10.1016/j.jnutbio.2017.12.004.
Interpretive Summary: Autoimmune disease, a kind of disease in which the body attacks its own tissue, is very common. Conventional therapies have limited effectiveness and often have significant side effects. Nutrition may provide an alternative and complementary approach to treating autoimmune disorders. Naturally occurring substances known as flavonoids, which help lower inflammation and may have the ability to protect cells from damage, are good candidates to test. In this study, using the Experimental Autoimmune Encephalomyelitis (EAE) mouse, which is a mouse model of human multiple sclerosis, we found that supplementing the mice's diet with dietary naringenin, a substance found naturally occurring in grapefruit, improved EAE symptoms and disease progression and its resulting damage. While the translational value of naringenin (from animals to humans) in clinical applications including both its effectiveness and safety will need to be determined in future intervention trials, our results indicate that naringenin may have potential as an alternative treatment to improve autoimmune disease by positively modifying the immune system's response.
Technical Abstract: Autoimmune disease is 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 the 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 the reduced immune cell infiltration and demyelination in the spinal cord. Additionally, the pro-inflammatory CD4 plus T cell subsets Th1, Th9, and Th17 cells together with their respective transcription factors T-bet, PU.1, and ROR gamma-t 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-alpha 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.