Hannaneh Roshanbakhsh - Student Research Committee, Damghan University, Damghan, Iran
Mahmoud Elahdadi Salmani - Department of Physiology, Faculty of Biology, Damghan University, Damghan, Iran
Fereshteh Pourabdolhossein - Department of Physiology, Faculty of Medical Sciences, Babol University of Medical Sciences, Babol, Iran

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease in the central nervous system. Hippocampal demylination and memory deficit are common in MS patients. Since oxidative stress and inflammatory factors are the most related pathophysiological cause of MS disease, the control of these factors could retard the disease progression and accelerate the myelin repair. Piperine has some anti-oxidants, anti-inflammatory and neuroprotective properties which can be a valuable candidate for preventing and improving MS symptoms. Here, we study the effect of piperine on spatial memory, myelin repair process and the gene expression level of inflammatory andanti-inflammatory cytokines, oxidative and antioxidant markers, brain derived neurotrophic factor (BDNF) and myelin basic protein. Materials and Methods: Adult male Wistar rats weighing 200–250 g in 7 experimental groups (n = 8) were studied. Demyelination was inducedby stereotaxic injection of lysolecithin (LPC) into the CA1 region of the hippocampus. The pre-treatment effect of piperine with a dose of 5 mg/kg and treatment after demyelination induction in doses of 5, 10 and 20 mg/kg on spatial memory was assessed by Morris water maze. Myelin repair process was analyzed with myelin specific staining. Real-time PCR technique was used to investigate the effect of piperine on IL-1β, TNF-α, NF-kB, FoxP3, IL-10, iNOS, Hmox-1, Nrf2, BDNF and MBP expression in the hippocampal tissue samples. Also, total antioxidant levels in tissue samples were measured by FRAP biochemical assay. Results: Piperine relatively improved the learning and spatial memory deficit in the LPC- induced demyelination model in the hippocampus. Histological findings also proved that the extent of demyelination was significantly decreased in the treatment and pretreatmentgroups with piperine. Treatment with piperine also reduced the expression level of the inflammatory cytokines (IL-1β, TNF-α, NF-kB) and increased the level of anti-inflammatory cytokines (FoxP3, IL-10). Piperine could negatively affect the expression level of iNOS and enhanced the level of antioxidant factors like Hmox-1 and Nrf2. The total antioxidant capacity of tissue was increased in piperine treated groups. Piperine also amplified the expression level of BDNF and MBP. Conclusion: Piperine has neuroprotective effect and can amplify the antioxidant and anti-inflammatory system which facilitates the myelin repair process. Furthermore, piperine improved spatial learning and memory deficit induced by hippocampal demyelination.