Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin-induced diabetic rats Nadia Mushtaq 1 , Roberta Schmatz 1 *, Luciane B. Pereira 1 , Mushtaq Ahmad 2 , Naiara Stefanello 1 , Juliano M. Vieira 1 , Fátima Abdalla 1 , Marília V. Rodrigues 1 , Jucimara Baldissarelli 1 , Luana Paula Pelinson 1 , Diéssica P. Dalenogare 1 , Karine Paula Reichert 1 , Eduardo M. Dutra 1 , Nádia Mulinacci 3 , Marzia Innocenti 3 , Maria Bellumori 3 , Vera Maria Morsch 1 and Maria Rosa Schetinger 1 * 1 Programa de Pós Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus Universitário, Santa Maria, RS, Brazil 2 Department of Biotechnology, University of Science and Technology, Bannu, Khyber Pakhtunkhwa, Pakistan 3 Department of NEUROFARBA, University of Florence, Sesto F.no (Firenze), Tuscany Italy We investigated the efficacy of rosmarinic acid (RA) in preventing lipid peroxidation and increased activity of acetylcholinesterase (AChE) in the brain of streptozotocin-induced diabetic rats. The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol and diabetic/RA 10 mg/kg. After 21 days of treatment with RA, the cerebral structures (striatum, cortex and hippocampus) were removed for experimental assays. The results demonstrated that the treatment with RA (10 mg/kg) significantly reduced the level of lipid peroxidation in hippocampus (28%), cortex (38%) and striatum (47%) of diabetic rats when compared with the control. In addition, it was found that hyperglycaemia caused significant increased in the activity of AChE in hippocampus (58%), cortex (46%) and striatum (30%) in comparison with the control. On the other hand, the treatment with RA reversed this effect to the level of control after 3 weeks. In conclu- sion, the present findings showed that treatment with RA prevents the lipid peroxidation and consequently the increase in AChE activity in diabetic rats, demonstrating that this compound can modulate cholinergic neurotransmission and prevent damage oxidative in brain in the diabetic state. Thus, we can suggest that RA could be a promising compound in the complementary therapy in diabetes. Copyright © 2013 John Wiley & Sons, Ltd. key words—streptozotocin; diabetes; lipid peroxidation; acetylcholinesterase; rosmarinic acid INTRODUCTION Diabetes mellitus, a major crippling disease refers to the group of diseases that lead to high blood glucose levels resulting from either low levels of the hormone (insulin) or from abnormal resistance to insulin’s effects. 1 The preva- lence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. 2 During diabetes, persistent hyperglycaemia causes the increased production of free radicals, as a result of glucose auto-oxidation and pro- tein glycosylation. 3,4 High level of lipid peroxidation has been found in diabetic patients. 3,4 Peroxidation of membrane lipids seriously impairs membrane functions and disturbs ionic gradient receptor and transport functions, results in cellular dysfunctions. 5,6 In addition, increased thiobarbituric acid reactive substances (TBARS) in rats with streptozotocin (STZ)-induced diabetes is a well-established method for monitoring lipid peroxidation. 7 It has been observed that reactive oxygen species contribute to the development of chronic complications in the brain. 8,9 Along with cerebrovascular disease, diabetes is implicated in the development of other neurological co-morbidities includ- ing alterations in neurotransmission, electrophysiological ab- normalities, structural changes and cognitive dysfunction. 10 Furthermore, diabetes has been implicated as a risk factor for dementia not only of vascular type but also to Alzheimer’s disease. 11 The exact pathophysiology of cognitive dysfunction and ce- rebral lesions in diabetes is not completely understood, but it is likely that hyperglycaemia, vascular disease, hypoglycaemia, insulin resistance and oxidative stress play significant roles. 12 Furthermore, some research using investigational diabetes established an increase in acetylcholinesterase (AChE) (3.1.1.7) activity, which may lead to alterations in cholinergic *Correspondence to: Dr Maria Rosa Schetinger, Departamento de Química/ Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil - 97105–900. E -mail: mariachitolina@gmail.com; Dr Roberta Schmatz, Departamento de Química/Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil - 97105–900. E-mail: betaschmatz@hotmail.com Received 4 June 2013 Revised 14 October 2013 Accepted 21 October 2013 Copyright © 2013 John Wiley & Sons, Ltd. cell biochemistry and function Cell Biochem Funct 2014; 32: 287–293. Published online 2 December 2013 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/cbf.3014