St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

Abstract

Multiple sclerosis (MS) is a central nervous system disorder mainly characterized by inflammation, demyelination and axonal injury. Anti-inflammatory agents can be used to ameliorate the disease process. Hypericum perforatum L or St. John's wort is widely used as an anti-depressant and antiinflammatory remedy in traditional and herbal medicine. Based on St. John's wort properties, the therapeutic potentials of an H. perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG 35-55 -induced experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Female C57BL/6 mice were immunized with specific antigen MOG 35-55 and then administered different doses of hyperforin or HPE postimmunization. Clinical symptoms/other relevant parameters were assessed daily. Histological analysis of the spinal cord was performed. T-cell proliferative activity was also evaluated using a BrdU assay. The effect of hyperforin on regulatory T-cells (T reg cells) was assessed using flow cytometry. The results indicate hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. The study also showed that hyperforin caused increased T reg cell levels in the spleen. These results indicated that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of T reg cell and could eventually be considered as a potential candidate for use in the treatment of MS. ARTICLE HISTORY

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

“…The same mice also had enhanced expression of IL-6, IL-17, and IL-23 and TF ROR-ct which conferred a pro-inflammatory T H 17-like phenotype. Surprisingly, the data with the medium-and high-dose estrogen mice showed significantly higher levels of T H 2 cell cytokines including IL-4 and IL-10 and T reg cell cytokines including IL-10 and TGF-b that antagonize T H 1 and T H 17 responses, respectively (Whitacre et al 1999;Nosratabadi et al 2015). A similar situation was previously described in female patients with MS, in whom regulatory cytokines like IL-4 and TGF-b were simultaneously up-regulated with IFN-c during disease progression (Pelfrey et al 2000;Rastin et al 2013).…”

Dicrocoelium ova can block the induction phase of experimental autoimmune encephalomyelitis

“…Each mouse received 200 µL of this emulsion through SC injection into two sites on its flank (100 µL/site). Each mouse also received 250 ng of pertussis toxin (Sigma, Germany) through IP injection on the day of immunization and 48 h later 19 . The animals were assessed clinically according to the standard criteria (0: normal; 1: loss of tail tone; 2: hind limb weakness; 3: hind limb paralysis; 4: hind limb and forelimb paralysis; and 5: moribund or dead 18 .…”

“…later. 19 The animals were assessed clinically according to the standard criteria (0: normal; 1: loss of tail tone; 2: hind limb weakness; 3: hind limb paralysis; 4: hind limb and forelimb paralysis; and 5: moribund or dead. 18 The clinical score, weight changes and incidence time of EAE were recorded in all groups each day to evaluate the pre-immunization and impact of Dicrocoelium eggs on EAE.…”

The Effect of Aerobic Training With the Consumption of Probiotics on the Myelination of Nerve Fibers in Cuprizone-induced Demyelination Mouse Model of Multiple Sclerosis

“…Many studies have documented that experimental autoimmune encephalomyelitis (EAE) is mediated by the Th1 and Th17 cells secreting pro-inflammatory cytokines (Kobayashi et al, 2010), while there is a relationship between disease recovery and the increased levels of Th2 cytokines (Nosratabadi, Rastin, Sankian, Haghmorad, Tabasi, et al, 2016). It seems that an upregulation of these cytokines in probiotic-treated mice stimulates a shift towards Th2 response which may be one of the mechanisms involved in the down-regulation of the autoimmune response.…”