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OBJECTIVE: To examine the effects of catalpol and rhein on pro-and anti-inflammatory responses in C57BL/6 mice with experimental autoimmune en-cephalomyelitis(EAE),a model of multiple sclerosis.METHODS: Female C57BL/6 mice were randomly divided into four groups(n = 30):(a)normal saline control,(b)EAE control,(c)EAE+prednisone ace-tate(PA,6 mg/kg),and(d)EAE+catalpol(40 mg/kg)and rhein(5 mg/kg).EAE was induced by injec-tion of myelin oligodendrocyte glycoprotein 35-55 plus pertussis toxin.Treatments were orally adminis-tered daily for 40 d.Disease progression and neuro-logical function were assessed using a semi-quanti-tative scale of tail and limb paralysis.Brains and spi-nal cords were collected on Days 6,20,and 40 and assessed for histopathological changes by hema-toxylin and eosin staining.Production of interleu-kin(IL)-2,IL-4,IL-10,and IL-17A protein was mea-sured by enzyme-linked immunosorbent assay.Ex-pression of the T helper(Th)1-,Th2-,Th17-,and reg-ulatory T cell(Treg)-specific transcription factors T-bet,GATA3,ROR-yt,and Foxp3,respectively,were analyzed by quantitative reverse-transcription poly-merase chain reaction and west blot analysis.RESULTS: Combination treatment with catalpol and rhein significantly alleviated the clinical disabil-ity and neurological dysfunction of mice with EAE.Catalpol and rhein treatment also reduced the infil-tration of pro-inflammatory T cells into pathologi-cal lesions; significantly increased the expression of the anti-inflammatory factors GATA3,Foxp3,IL-4,and IL-10; and significantly decreased the expres-sion of the pro-inflammatory factors T-bet,ROR-yt,IL-2,and FL-17A.CONCLUSION: Catalpol and rhein reduced the neu-rological disabilities of mice with EAE,at least in part by rebalancing the pro-and anti-inflammatory environment in the brains and spinal cords.