Comparison the Effects of Hesperetin and Hesperetin-NPs on Gene Expression and Microglia Activities Following Demyelination Process in Focal Demyelination Model of Multiple Sclerosis

Demyelination and disturbance of action potential conductance are regarded as main signs of Multiple Sclerosis(MS). More than 70% percent of patients show visual disorder as the earliest symptoms of MS. Although hesperetin (Hst) has been introduced as effective anti-inflammatory agent in treatment of several inflammatory disorders, but because of low water solubility, its clinical application has been limited. The present study design to evaluate the effects of hesperetin and hesperetin NPs on gene expression, myelin repairand microglia activation in lysolecithin (LPC)-induced demyelination. Materials and Methods: Demyelination process started with injection of LPC (1%, 2μL) into rat optic chiasm. Animals have received oral administration of Hst and Hst NPs at dose of 20 mg/kg for 14 or 21days’ post lesion. Visual evoked potential (VEPs) records were used to assess the functional property of the optic pathway on days 0, 7, 14 and 21 post lesions. Immunostaining against Iba 1 (Microglia marker) was carried out for evaluation of inflammation level and glial activation. we measured expressions of MBP (Myelin Basic Protein) mRNAs for determination of remyelination processes. Results: Electrophysiologicalevidence demonstrated that oral administration of Hst and Hst NPs could reduce the P1-N1 waves compared to the LPC groups .Immunostaining showed oral administration of Hst NPs effectively ameliorated microglia activation and level of inflammation in opticchiasm area. Results of Real Time PCR indicated that .remyelination process enhanced in the optic chiasm following administration of Hst NPs. Conclusion: Overall, our findings indicate that hesperetin NPs could remarkably enhance the functional recovery of the opticpathway by its protective effects on myelin sheath, attenuation of glial activation and increase of MBP expression.