Experimental Study Of Salvianolic Acid B In The Treatment Of Experimental Autoimmune Encephalomyelitis

Background:Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases of the central nervous system (CNS) which mediated by both Thl and Th17 cells. It is thought that, in the initial stage of MS, myelin-reactive CD4+ T cells activated in the periphery infiltrate into the CNS, followed closely by a broad range of other immune cells, including T cells, macrophages, dendritic cells (DCs), B cells, and neutrophils. Once in the CNS, myelin-reactive T cells become reactivated and produce pro-inflammatory mediators, which induce chemokine secretion by CNS resident cells, thus recruiting more inflammatory cells from the periphery and triggering an immunologic cascade that results in myelin damage. While it appears that both IFN-γ-producing Thl and IL-17-producing Th17 cells play important roles in EAE pathogenesis, the mechanisms by which autoreactive Th cells initiate the disease process remain only partially understood. There is no cure for multiple sclerosis. Treatments attempt to improve function after an attack and prevent new attacks. Nowadays, the disease modifying treatments for multiple sclerosis were mainly based on immune regulation or immune suppression. During symptomatic attacks, high doses of corticosteroids is the usual therapy in China. As a lifelong disease once suffered, the long-term drug administration is needed. These long term treatments will lead to adverse effects, expensive therapeutic costs and are poorly tolerated. Thus it is still be urgent and necessary to seek cheaper and well-tolerated disease modifying drugs for MS treatment. Salvianolic acid B (Sal B) is one of the major water-soluble bioactive components of Traditional Chinese herb, Salvia miltiorrhiza Bunge. It has exerted multiple bioactivities through its nti-oxidative and anti-inflammatory effects.Objective:To test if Sal B can ameliorate EAE through its anti-inflammatory effects.Methods and results:1. Intraperitoneal Sal B administration reduce disease severity of EAE. It decreased the clinical score and disease incidence and protected disease mediated body loss when compared with control;2. H&E staining showed that there are less inflammation in Sal B treated group than in control group, and the total mononuclear cell number in spinal cord of EAE mice was significantly decreased by Sal B administration. In addition, The immunohistochemical staining of CD45 in spinal cord was used to show the infiltrated CD45+ leukocytes. It was shown that in the Sal B treated group, there are very fewer CD45+ cells than the control group;3. Astrogliosis and microglia/macrophages activation or proliferation are two major pathophysiological characters in EAE development. There were fewer GFAP+ astrocytes in Sal B treated group than in control group, suggesting that Sal B treatment effective inhibit astrogliosis during EAE development. As to microglia/macrophages, there were a slightly fewer Iba-1+ cells in Sal B treated group;4. Although a tendency of fewer CD4+ T cells in the spinal cord of Sal B treated group when compared with control group, there is no significant difference of CD4+ T in spinal cord between groups. However the percentage of CD4+ T cells in mononuclear cells of spleen was greatly decreased after Sal B treatment. The introcellular staining showed that Thl cells were specifically suppressed by Sal B, while the Th17 cell frequency remain unchanged between Sal B treated and control group;Conclusions:Sal B inhibit Thl responses other than Th17 responses in EAE. Thus our data implied that Sal B may serve as an effective therapeutic agent for MS/EAE treatment through inhibiting Thl cell responses..