Diene Valepotriates from Valeriana glechomifolia Prevent Lipopolysaccharide-Induced Sickness and Depressive-Like Behavior in Mice.

Liz G Müller,Alice F Viana,Ana Paula Ravazzolo,Stela Maris K Rates,Eveline D Stolz,Milene Borsoi,Vivian Herzfeldt

doi:10.1155/2015/145914

Abstract

Valeriana glechomifolia, a native species from southern Brazil, presents antidepressant-like activity and diene valepotriates (VAL) contribute to the pharmacological properties of the genus. It is known that depression can develop on an inflammation background in vulnerable patients and antidepressants present anti-inflammatory properties. We investigated the effects of VAL (10 mg/kg, p.o.) on sickness and depressive-like behaviors as well as proinflammatory cytokines (IL-1β and TNF-α) and BDNF expression in the cortex of mice exposed to a 5 min swimming session (as a stressful stimulus) 30 min before the E. coli LPS injection (600 µg/kg, i.p.). The forced swim + LPS induced sickness and depressive-like behaviors, increased the cortical expression of IL-1β and TNF-α, and decreased BDNF expression. VAL was orally administered to mice 1 h before (pretreatment) or 5 h after (posttreatment) E. coli LPS injection. The pretreatment with VAL restored the behavioral alterations and the expression of cortical proinflammatory cytokines in LPS-injected animals but had no effects on BDNF expression, while the posttreatment rescued only behavioral alterations. Our results demonstrate for the first time the positive effects of VAL in an experimental model of depression associated with inflammation, providing new data on the range of action of these molecules.

Highlights

Major depressive disorder (MDD) is a recurrent and incapacitating mood disorder being related to high mortality and morbidity [1]
Considering the above mentioned data, in the present study we investigated the effects of a diene valepotriates fraction (VAL) obtained from V. glechomifolia on sickness and depression-like behavior triggered by intraperitoneal administration of E. coli LPS, in mice previously submitted to a forced swimming session as a stressful stimulus [13]
The present study demonstrated the positive effects of Valeriana glechomifolia diene valepotriates (VAL) in an animal model of depression that correlates the activation of inflammatory pathways with the manifestation of depression-like behavior

Summary

Introduction

Major depressive disorder (MDD) is a recurrent and incapacitating mood disorder being related to high mortality and morbidity [1]. The identification of novel biological targets and pathways that may play a role in MDD pathophysiology is required. In this regard, several studies have been pointing to the association of the immune system activation with MDD [3, 4]. Of note, depressed patients display elevated plasma levels of proinflammatory cytokines such as interleukin- (IL-) 1β, IL-6, and tumor necrosis factor-alpha (TNF-α) [2, 5,6,7]. As well as increased expression of proinflammatory cytokines in frontal cortex [8]. Some studies showed that the association of anti-inflammatories to conventional antidepressants increased the efficacy of these drugs [9,10,11]

Results

Discussion

Conclusion