ORIGINAL ARTICLE Morus nigra and its major phenolic, syringic acid, have antidepressant-like and neuroprotective effects in mice Ana Paula Dalmagro 1,2 & Anderson Camargo 2 & Ana Lúcia Bertarello Zeni 1,2 Received: 6 February 2017 /Accepted: 11 August 2017 # Springer Science+Business Media, LLC 2017 Abstract Depression is a disorder with a high incidence that has been increasing worldwide although the patho- physiology remains unclear. Moreover, some studies re- vealed a higher concentration of glutamate and oxidative stress in the patients’ brain, which causes cell death by excitotoxicity. Morus nigra L. is known as black mulberry and its leaves are popularly used to treat affections related to menopause, obesity and high cholesterol. M. nigra leaves are a rich fount of phenolics which well-known by the antioxidant property. Herein, we examined the phenolic profile and the antidepressant-like effect of the Morus nigra aqueous extract (MN) and its major phenolic constit- uent, syringic acid (SA). Furthermore, the involvement of antioxidant and neuroprotective activities were further evaluated. Our results show that acute and subchronic MN or SA administration exerted antidepressant-like prop- erty in the behavioral testes in mice. The results suggest that the antidepressant-like effect of MN, at least in part, could be due to the SA influence. Moreover, the observed effect involves the nitro-oxidative system modulation in both the serum and brain of mice. Furthermore, MN or SA was able to contain the glutamate-induced cell death in the hippocampal and cortical slices implicating the neu- roprotection activity in the antidepressant-like effect. Keywords Morus nigra . Antidepressant . Neuprotective . Syringic acid Introduction Depression is a common, recurrent and incapacitating disorder with a high incidence worldwide (Berton and Nestler 2006). Despite the approached efforts, the influence of brain oxidative stress in the illness mechanism has not been entirely explained. Although, it is established that reactive oxigen species (ROS) is implicated in the depression pathophysiology (Lee et al. 2013; Lucca et al. 2009; Maes et al. 2011), causing damage to DNA, lipids and proteins (Pandya et al. 2013). Therefore, leading to cell death and decreasing neurogenesis (Maes et al. 2011). The symptons have been extensively associated with the features of an inflammatory response, regarding an increased expression of proinflammatory cytokines and their receptors, including the raise of chemokines and soluble adhesion molecules levels (Maes 1999; Miller et al. 2009). Some studies suggest that hypercholesterolemia is also related to depression (Tyrovolas et al. 2009; Davison and Kaplan 2012). Recently, Engel et al. (2016) demonstrated that hypercholesterolemic mice presented antidepressant-like effect with alterations in the monoaminergic system. Previously, Tedders et al. (2011) and Wysokinski et al. (2015) showed an association between low HDL-cholesterol level and a severe depression. The most common treatments for depression are related to the monoaminergic system, moreover, the therapy has also been improved concerning glutamatergic system with the an- tagonist of N-Methyl-D-Aspartate (NMDA) receptor, as the ketamine (Salat et al. 2015). In this regard, post mortem studies revealed higher concentration of glutamate in the patient’ s brain (Hashimoto et al. 2007) evidencing a link between hyperacti- vation of NMDA receptor and cell death by excitotoxicity. * Ana Lúcia Bertarello Zeni anazeni@furb.br; zeni.ana@gmail.com 1 Programa de Pós-Graduação em Química, Departamento de Química, Universidade Regional de Blumenau, Blumenau, Santa Catarina CEP 89030-903, Brazil 2 Laboratório de Avaliação de Substâncias Bioativas, Departamento de Ciências Naturais, Universidade Regional de Blumenau, CEP 89030-903, Campus I, Blumenau, SC 89012-900, Brazil Metab Brain Dis DOI 10.1007/s11011-017-0089-y