Research ReportsA valepotriate-enriched fraction from Valeriana glechomifolia decreases DNA methylation and up-regulate TrkB receptors in the hippocampus of miceMüller, Liz G.a; Biojone, Carolineb; Sales, Amanda J.b; Betti, Andresa H.a; Herzfeldt, Viviana; Joca, Sâmia R.L.b,,c; Rates, Stela M.K.a Author Information aFaculty of Pharmacy, Laboratory of Experimental Psychopharmacology, Graduate Studies Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre – RS bLaboratory of Psychopharmacology, School of Pharmaceutical Sciences from Ribeirão Preto, University of São Paulo, Ribeirão Preto – SP cCenter for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Ribeirão Preto – SP, Brazil Received 8 February 2019 Accepted as revised 12 November 2019 Correspondence to Liz G. Müller, PhD, Faculdade de Farmácia – UFRGS, Avenida Ipiranga, 2752, Porto Alegre – RS 90610000, Brazil, E-mail: [email protected] Behavioural Pharmacology: June 2020 - Volume 31 - Issue 4 - p 333-342 doi: 10.1097/FBP.0000000000000534 Buy Metrics Abstract DNA methylation, an epigenetic modification that mediates gene silencing, has been shown to play a role in the neurobiology of major depression. Studies suggested that terpenes inhibit DNA methylation and increase gene expression. The present study investigated the involvement of DNA methylation in the antidepressant-like activity of diene valepotriates, non-glicosilated carbocyclic iridoids that comprise a family of terpenes obtained from Valeriana glechomifolia. The antidepressant-like effect of diene valepotriates acute administration (5 mg/kg, p.o.) in mice submitted to the forced swimming test was followed by a decrease in global DNA methylation in animals’ hippocampus (but not in the pre-frontal cortex). Mice pretreatment with anysomicin (a protein synthesis inhibitor) and K252a (an inhibitor of Trk receptors) attenuated diene valepotriates-induced antidepressant-like effect in the forced swimming test. Diene valepotriates elicited an upregulation in the TrkB receptor and a tendency to increase BDNF levels in mice hippocampus. These results demonstrate that DNA methylation could be an in vivo molecular target of diene valepotriates. The diene valepotriates-triggered reduction in hippocampal DNA methylation is accompanied by increased protein synthesis, which is involved in its antidepressant-like activity. Furthermore, BDNF-mediated TrkB signaling may contribute for diene valepotriates antidepressant-like effect. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.