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T cell infiltration into the CNS is a significant underlying pathogenesis in autoimmune inflammatory demyelinating diseases. Several lines of evidence suggest that glutamate dysregulation in the CNS is an important consequence of immune cell infiltration in neuroinflammatory demyelinating diseases; yet, the causal link between inflammation and glutamate dysregulation is not well understood. A major source of glutamate release during oxidative stress is the system Xc− transporter; however, this mechanism has not been tested in animal models of autoimmune inflammatory demyelination. We find that pharmacological and genetic inhibition of system Xc− attenuates chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE). Remarkably, pharmacological blockade of system Xc− 7 d after induction of EAE attenuated T cell infiltration into the CNS, but not T cell activation in the periphery. Mice harboring a Slc7a11 (xCT) mutation that inactivated system Xc− were resistant to EAE, corroborating a central role for system Xc− in mediating immune cell infiltration. We next examined the role of the system Xc− transporter in the CNS after immune cell infiltration. Pharmacological inhibitors of the system Xc− transporter administered during the first relapse in a SJL animal model of relapsing-remitting EAE abrogated clinical disease, inflammation, and myelin loss. Primary coculture studies demonstrate that myelin-specific CD4+ Th1 cells provoke microglia to release glutamate via the system Xc− transporter, causing excitotoxic death to mature myelin-producing oligodendrocytes. Taken together, these studies support a novel role for the system Xc− transporter in mediating T cell infiltration into the CNS as well as promoting myelin destruction after immune cell infiltration in EAE.

Psoralea corylifolia (PC), a medicinal plant, is used in traditional medicine to treat diabetes. Purpose of the research was to examine the antidiabetic and antilipemic potential of PC and to determine the relationship between its antidiabetic potential and the trace elements present. Wistar rats (150–200 g) with fasting blood glucose (FBG) of 80–110 mg dl−1(sub-diabetic) and 150–200 mg dl−1(mild diabetic) were selected for the short term antidiabetic studies and severely diabetic rats (FBG > 300 mg dl−1) were chosen for the long term antidiabetic and hypolipemic studies of PC seed extract. Laser induced breakdown spectroscopy (LIBS) was used to detect trace elements in the PC extract and the intensity ratios of trace elements were estimated. The dose of 250 mg kg−1 of PC extract was found to be the most effective in lowering blood glucose level (BGL) of normal, sub, mild and severely diabetic rats during FBG and glucose tolerance test (GTT) studies. Lipid profile studies on severely diabetic rats showed substantial reduction in total cholesterol, triglycerides, very low density lipoprotein, and low density lipoprotein and an increase in the total protein, body weight, high density lipoprotein, and hemoglobin after 28 days of treatment. Significant reduction in urine sugar and protein levels was also observed. LIBS analysis of the PC extract revealed the presence of Mg, Si, Na, K, Ca, Zn and Cl. The study validates the traditional use of PC in the treatment of diabetes and confirms its antilipemic potential. The antidiabetic activity of PC extract may partly be due to the presence of appreciable amounts of insulin potentiating elements like Mg, Ca, and K.