Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Beneficial effects of oral administration of C-Phycocyanin and Phycocyanobilin in rodent models of experimental autoimmune encephalomyelitis Majel Cervantes-Llanos a,1 , Nielsen Lagumersindez-Denis b,1 , Javier Marín-Prida b,1 , Nancy Pavón-Fuentes c , Viviana Falcon-Cama a , Beatriz Piniella-Matamoros a , Hanlet Camacho-Rodríguez a , Julio Raúl Fernández-Massó a , Carmen Valenzuela-Silva a , Ivette Raíces-Cruz a , Eduardo Pentón-Arias a,e , Mauro Martins Teixeira d , Giselle Pentón-Rol a, ⁎ a Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, Havana, PO Box 6162, Cuba b Center for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, Havana, PO Box 430, Cuba c International Center for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160, Playa, Havana, PO Box 11300, Cuba d Laboratory of Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, Brazil e Latin American School of Medicine (ELAM), Carretera Panamericana Km 3½, Sta. Fe, Playa, PO Box 19108, Havana, Cuba ARTICLE INFO Keywords: Multiple sclerosis Experimental autoimmune encephalomyelitis C-Phycocyanin Phycocyanobilin Remyelination ABSTRACT The only three oral treatments currently available for multiple sclerosis (MS) target the relapsing forms of the disease and concerns regarding efficacy, safety and tolerability limit their use. Identifying novel oral disease- modifying therapies for MS, targeting both its inflammatory and neurodegenerative components is still a major goal. Aim: The scope of this study was to provide evidence that the oral administration of C-Phycocyanin (C-PC), the main biliprotein of the Spirulina platensis cyanobacteria and its tetrapyrrolic prosthetic group, Phycocyanobilin (PCB), exert ameliorating actions on rodent models of experimental autoimmune encephalomyelitis (EAE). Main methods: EAE was induced in Lewis rats using the spinal cord encephalitogen from Sprague Dawley rats and in C57BL6 mice with MOG 35–55 peptide. Clinical signs, motor function, oxidative stress markers, cytokine levels by ELISA and transmission electron microscopy analysis were assessed. Key findings: Either prophylactic or early therapeutic administration of C-PC to Lewis rats with EAE, significantly improved clinical signs and restored the motor function of the animals. Furthermore, C-PC positively modulated oxidative stress markers measured in brain homogenate and serum and protected the integrity of cerebral myelin sheaths as shown by transmission electron microscopy analysis. In C57BL/6 mice with EAE, PCB orally improved clinical status of the animals and reduced the expression levels of brain IL-6 and IFN-γ proinflammatory cyto- kines. Significance: These results, for the first time, support the fact that both C-PC and PCB administered orally could potentially improve neuroinflammation, protect from demyelination and axonal loss, which may be translated into an improved quality of life for MS patients. 1. Introduction Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) with a possible autoimmune etiology [1]. The prolonged use of the currently approved drugs mainly due to the chronicity of MS, as well as the https://doi.org/10.1016/j.lfs.2017.12.032 Received 29 September 2017; Received in revised form 20 December 2017; Accepted 23 December 2017 ⁎ Corresponding author at: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box: 6162, Havana 10 600, Cuba. 1 Majel Cervantes-Llanos, Nielsen Lagumersindez-Denis and Javier Marín-Prida contributed equally to this work. E-mail address: giselle.penton@cigb.edu.cu (G. Pentón-Rol). URL: http://www.cigb.edu.cu (G. Pentón-Rol). Abbreviations: AUC, area under the curve; BR, bilirubin; BV, biliverdin; BVR, biliverdin reductase; CI, confidence interval; CNS, central nervous system; C-PC, C-Phycocyanin; EAE, experimental autoimmune encephalomyelitis; MS, Multiple sclerosis; PCB, Phycocyanobilin; pro, prophylactic; ther, therapeutic Life Sciences 194 (2018) 130–138 Available online 27 December 2017 0024-3205/ © 2017 Published by Elsevier Inc. T