Therapeutic Effects Of Diosgenin In Experimental Autoimmune Encephalomyelitis

Multiple sclerosis(MS)is a chronic autoimmune demyelinating disease of the central nervous system,affecting more than 2.3 million people worldwide.With the continuous development of MS research,MS has been defined more precisely.At present,MS is considered as an autoimmune chronic inflammatory disease in central nervous system(CNS),which is affected by genes,environment and other factors and,thus,is a heterogeneous disease.The FDA approved 14 MS drugs.Most of the drugs are used in the treatment of relapse-remitting MS and they have no curative effect in patients with progressive MS.Currently there is only one drug for the treatment of progressive MS.Normally,MS was divided into four types,relapse-remitting MS(RRMS),secondary progressive MS(SPMS),primary progressive MS(PPMS),progress relapsing MS(similar to the SPMS and PPMS).Their symptoms,course of illness and treatment are not the same.Pathologic features of progressive MS include atrophy of the brain due to axon loss,cortical demyelination,glial cell activation and myelin regeneration disorder.People with progressive MS experience physical decline and disability.Progressive MS includes secondary progressive MS and primary progressive MS.Clinical studies have shown that in most cases primary progressive MS is only a form of secondary progressive MS in which the remitting stage is subclinical.In the central nervous system of MS patients,immune cells including microglia and astrocytes,and B cell produced by ectopic germinal center,drive progressive MS and cause neural degenerative diseases.These immune-dependent factors may activate multiple disease processes,and then self-perpetuate and act on neurons with immune independent toxic mechanisms.The treatment of RRMS have made significant progress,more than 10 FDA-approved drugs for the treatment of RRMS target the immune system.In general,these immune-modulators can reduce the number of Th1/Th17 cells that cause disease,induce Treg cells,influence the recruitment of inflammatory cells to the nervous system,or act on B cells.There is no clinical medicine to cure the disease.Steroid hormones have ameliorating effects in multiple sclerosis and experimental autoimmune encephalomyelitis models.Glucocorticoid is a powerful immunosuppressant that has strong inhibitory effect to inhibit experimental autoimmune encephalomyelitis and acute relapsing period in the treatment of MS patients,but the negative impact of its long-term adminstration is obvious.As a possible treatment options for MS,estrogen and progesterone attracted many attention.Studies have shown that,there is a negative correlation between plasma levels of these hormones and the severity of the symptoms of MS patients.Diosgenin is a plant-derived steroid.Previous studies in our laboratory have shown that diosgenin can promote the differentiation of oligodendrocyte precursor cells and accelerate the myelin processes.In this study,we found that diosgenin can dose dependently slow down the progression of experimental autoimmune encephalomyelitis mice,reduce inflammation in the central nervous system of the experimental animals,and reduce its demyelinating area in the central nervous system of the experimental animals.Moreover,we also found that the treatment with diosgenin can significantly inhibit the activation of microglia/macrophages,reduce the proliferation of CD4+ T cells,and hinder the differentiation of Th1/Th17 cells.Therefore,we believe that diosgenin may develop into a potential drug for the treatment of inflammatory demyelinating diseases such as MS.