Protective effects of catalpol and rhein in murine experimental autoimmune encephalomyelitis via regulation of T helper (Th) 1, Th2, Th17, and regulatory T cell responses.

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 acetate (PA, 6 mg/kg), and (d) EAE + catalpol (40 mg/ kg) and rhein (5 mg/kg). EAE was induced by injection of myelin oligodendrocyte glycoprotein 35-55 plus pertussis toxin.Treatments were orally administered daily for 40 d. Disease progression and neurological function were assessed using a semi-quantitative scale of tail and limb paralysis. Brains and spinal cords were collected on Days 6, 20, and 40 and assessed for histopathological changes by hematoxylin and eosin staining. Production of interleukin (IL)-2, IL-4, IL-10, and IL-17A protein was measured by enzyme-linked immunosorbent assay. Expression of the T helper (Th)1-, Th2-, Th17-, and regulatory T cell (Treg)-specific transcription factors T-bet, GATA3, ROR-gamma t, and Foxp3, respectively, were analyzed by quantitative reverse-transcription poly-merase chain reaction and western blot analysis. RESULTS: Combination treatment with catalpol and rhein significantly alleviated the clinical disability and neurological dysfunction of mice with EAE. Catalpol and rhein treatment also reduced the infiltration of pro-inflammatory T cells into pathological lesions; significantly increased the expression of the anti-inflammatory factors GATA3, Foxp3, IL-4, and IL-10; and significantly decreased the expression of the pro-inflammatory factors T-bet, ROR-gamma t, IL-2, and IL-17A. CONCLUSION: Catalpol and rhein reduced the neurological disabilities of mice with EAE, at least in part by rebalancing the pro- and anti-inflammatory environment in the brains and spinal cords. (C) 2019 JTCM. All rights reserved.