title: Hesperidin ameliorates immunological outcome and reduces neuroinflammation in the mouse model of multiple sclerosis.
abstract: Multiple sclerosis (MS) is the most abundant central nervous system (CNS) inflammatory disease, which is due to the reaction of auto reactive T cells with own myelin proteins, leading to physical disorder and paralysis among people suffering the disease. Hesperidin, a flavanone glycoside found abundantly in citrus fruits possesses a wide range of pharmacological properties including potential anti-inflammatory and anti-cancer effects. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of hesperidin on MS alleviation. Female C57BL/6 mice were immunized with MOG35-55. Clinical scores and other parameters were monitored daily for the 21days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T cell differentiation was evaluated via flow cytometry. The results demonstrated that hesperidin inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. Hesperidin increased Treg cells production of interleukin IL-10 and transforming growth factor (TGF)-β, but concurrently resulted in a significant reduction in production of IL-17 and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of Th17 cells, as well as significant increase in percentages of Treg cells in the spleen and lymph nodes. Real-time PCR results indicated hesperidin treatment reduced ROR-γt factor expression, but enhanced Foxp3 expression. Collectively, these results demonstrated that hesperidin could reduce the incidence and severity of disease.
authors.affiliation: Department of Laboratory Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran; Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Dariush
authors.initials: D
authors.lastname: Haghmorad
authors.affiliation: Department of Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Mohammad Bagher
authors.initials: MB
authors.lastname: Mahmoudi
authors.affiliation: Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Salehipour
authors.affiliation: Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Zoleikha
authors.initials: Z
authors.lastname: Jalayer
authors.affiliation: Nanotechnology Research Center, BuAli Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir Abbas
authors.initials: AA
authors.lastname: Momtazi Brojeni
authors.affiliation: Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rastin
authors.affiliation: Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Parviz
authors.initials: P
authors.lastname: Kokhaei
authors.affiliation: Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: mahmoudim@mums.ac.ir.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mahmoudi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006569:Hesperidin / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D006569:Hesperidin
keywords: Central nervous system; Experimental autoimmune encephalomyelitis; Hesperidin; Multiple sclerosis