Biomedicine& PreventiveNutrition 3 (2013) 26–30 Original article Treatmentwith 7-O-tetradecanoyl-genistein reducesIFN-␥ and IL-17 levels in the brain and amelioratesclinical signs of experimental autoimmune encephalomyelitis SandraB.R.Castro a , Celso O. RezendeJunior b , Caio C.S. Alves a , Alyria T. Dias a , Lívia L. Alves a , Mauro V. Almeida b , Maria AparecidaJuliano c , Henrique C. Teixeira a , Ana Paula Ferreira a,∗ a Departamento deParasitologia, Microbiologiae Imunologia, Universidade Federal deJuiz deFora,rua JoséLourenc¸ o Kelmer s/n,36036-900 Juiz deFora,Minas Gerais, Brazil b Departamento deQuímica, Universidade Federal deJuiz deFora,Juiz deFora,Minas Gerais, Brazil c Departamento deBiofísica, Universidade Federal deSãoPaulo,SãoPaulo, Brazil a r t i c l e i n f o Articlehistory: Received10 March 2011 Accepted22 June 2011 Keywords: EAE Multiple sclerosis Genistein a b s t r a c t Experimental autoimmuneencephalomyelitis (EAE) is a murine autoimmunedisease usedto studymulti- ple sclerosis(MS), a human inflammatorydemyelinatingdisease of the centralnervoussystem. Genistein treatmentis known to reverseclinical signs of EAE. The present work investigates the use of a genistein analog 7-O-tetradecanoyl-genistein (TDG) in the treatment of EAE. In this study, the genistein analog TDG was obtainedby the esterificationreactionof genistein.The molecule of TDG was developedbased on this previousknowledge,using esterificationin vitroto bypassthe in vivoprocessingwhich favorsthe biological activity and increasinglipid solubility. The results show that TDG treatmentpromotesreduc- tion of the clinical signs in EAE animalsand it correlates with lower levelsof TGF-␥, IL-6, IL-17 and IFN-␥ in the brain. ©2012 Published by Elsevier Masson SAS. 1. Introduction Multiple sclerosis (MS) is a chronic inflammatory demyelinat- ing disorder that affects the central nervous system (CNS) [1,2]. Experimental autoimmune encephalomyelitis (EAE) is a model for the study of MS. For a long time cytokines produced by Th1 cells were considered primarily responsible for the induction of inflammation in CNS during the developmentof MS and EAE [3,4]. Recently, the importance of Th17 cells has been identified in this process[5,6]. Genistein is an isoflavonoid compound derived from soy that can affect many different cellular mechanisms such as the inhi- bition of tyrosine kinases. It increases the activity of antioxidant enzymes and decreases the production of pro-inflammatory molecules by an inhibitory effect on the classical NF-␥B activation factor, known to play a role in inflammation, immune modulation and cell proliferation [7–9]. Genistein has been shown to down- modulate pro-inflammatory cytokines like IFN-␥, IL-12 and TNF-␣, and to reverse clinical signs of EAE [10]. Although genistein has potential clinical application, it has disadvantagesrelated to its chemical structure, such rapid in vivo metabolism [11–13]. The ∗ Correspondingauthor. Tel.: +5532 21023214;fax: +5532 21023214. E-mail address: ana.paula@ufjf.edu.br (A.P. Ferreira). esterification in vivo of genistein could be responsible for the increase of biological activity [14]. Besides this, correlation between the hydrophobic character of genistein, membrane permeability and biological activity is frequently observed[11,15]. The molecule of 7-O-tetradecanoyl-genistein (TDG) was developed based on this previous knowledge, using esterification in vitro to bypass the in vivo processing which favors the biological activity and increasinglipid solubility [16]. Thus, the aim of this study was to evaluateTDG’seffect on cytokine modulation in the EAE model. 2. Materials and methods 2.1. Chemical compounds The novel genistein analog TDG was synthesized as shown in Fig. 1. The genistein ester can be easily obtained, in high yield, by the esterification reaction of genistein with tetradecanoicacid in presence of dicyclohexylcarbodiimide (DCC) and dimethy- laminopyridine (DMAP) in dichloromethane. Genistein (Sigma, St. Louis, MO, USA) and its analog TDG were solubilized in the DMSO (Sigma), never exceeding0.1%(v/v), and diluted in sterile phosphate buffered saline (PBS). The partition coefficient P [log (P)] of genistein (1.67) and TDG (6.69) representsthe hydrophobic properties of thesecompounds. 2210-5239/$– seefront matter ©2012Publishedby Elsevier Masson SAS. doi:10.1016/j.bionut.2011.06.023 RETRACTED