Rhodioloside ameliorates depressive behavior via up-regulation of monoaminergic system activity and anti-inflammatory effect in olfactory bulbectomized rats
Introduction
Rhodioloside (RH) (p-hydroxy-phenethyl-β-D-glucoside, C14H20O7, Fig. 1) is a major bioactive marker substance in the standardized extracts (SHR-5) from Rhodiola rosea. And Rhodiola rosea (also known as golden root) is mentioned as the most commonly used psychostimulant for a range of conditions such as depression and anxiety, fatigue, anaemia etc. in the Europe and Asia [1], [2]. Previous studies showed that RH has lots of biological activities such as anti-stress, anti-fatigue and anti-oxidative [3], [4], [5], and RH also have antidepressant-like effect on behavior in rats [6], [7]. Moreover, another recent report showed that RH could improve LPS-induced depressive behavior in mice [8]. These evidences indicated that RH might become a potential therapeutic agent for depression. However, its antidepressant effects and mechanisms remain unclear as yet.
It is widely accepted that a defect in monoamine system plays an important role in the pathogenesis of OBX-induced depression, especially the reduction of neurotransmitters such as serotonin (5-HT) and norepinephrine (NE) levels, which are qualitatively similar to those occurring in patients with major depression [9], [10]. The abnormalities in the monoaminergic system were most apparent in the prefrontal cortex (PFC) of OBX rats, and could be reversed by chronic antidepressant treatments [11]. It has also been reported that activation of inflammatory responses and release of pro-inflammatory cytokines (PICs) were increased by OBX and decreased by antidepressant treatment [12], which indicated that inflammation may be involved in the therapeutic action of antidepressants.
In this study, the OBX model, a well-documented animal model for evaluating antidepressant action of compounds, was used to investigate the antidepressant-like effect of RH. Furthermore, the possible molecular mechanisms were clarified by measuring the 5-HT and NE levels, IL-1β and IL-6 levels, p-NF-kB P65 protein expression in PFC of OBX rats.
Section snippets
Animals
Male Sprague-Dawley rats weighting 200–220 g were from the Laboratory Animal Center of Zhejiang Province, China. The animals were kept in polypropylene cages remained at 22 ± 1 °C temperature and 12-h light/dark cycle with free access to food and water. All procedures and animal welfare were performed strongly in agreement with the National Institute of Health Guide (NIH publication No. 80–23, revised 1996) and the PR China legislation for the care and use of laboratory animals.
Drugs
Rhodioloside (RH)
Effects of RH on sucrose intake in SPT
Sucrose preference is a measure of anhedonia. As shown in Fig. 2, there were no significant difference between groups during the pretest [F(4,35) = 0.0813, p > 0.05]. At the end of recovery phase, OBX rats showed a noteworthy reduction in sucrose intake compared with sham-operated rats [F(4,35) = 18.070, p < 0.01]. Administration of AMI (10 mg/kg) (p < 0.01) or RH (20, 40 mg/kg) (p < 0.05, p < 0.05, respectively) for 1 week (in the 3th week after OBX surgery) improved the lower sucrose consumption in OBX group
Discussion
Surgical ablation of bilateral olfactory bulbs has been widely proven as a reliable and valuable animal model of depression. OBX induces numerous behavior changes, including hyperactivity, increased despair behavior, and anhedonia symptoms. Interestingly, these behavioral abnormalities are not related to anosmia [15], but may rely on the disrupted connections in the olfactory-limbic circuitry and enlarged third ventricles [16]. These alterations are similar to those observed in patients with
Conflict of interest
There is no conflict of interest.
References (21)
- et al.
The effectiveness and efficacy of Rhodiola rosea L.: a systematic review of randomized clinical trials
Phytomedicine
(2011) Adaptogens in mental and behavioral disorders
Psychiatr. Clin. North Am.
(2013)- et al.
Comparative study of Rhodiola preparations on behavioral despair of rats
Phytomedicine
(2008) - et al.
Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats
Pharmacol. Biochem. Behav.
(2014) - et al.
Salidroside attenuates lipopolysaccharide (LPS) induced serum cytokines and depressive-like behavior in mice
Neurosci. Lett.
(2015) - et al.
The olfactory bulbectomized rat as a model of depression: an update
Pharmacol. Ther.
(1997) - et al.
The olfactory bulbectomised rat as a model of depression
Neurosci. Biobehav. Rev.
(2005) - et al.
Quercetin suppress microglial neuroinflammatory response and induce antidepressent-like effect in olfactory bulbectomized rats
Neuroscience
(2013) - et al.
Antidepressant-like effects of the saponins extracted from Chaihu-jia-longgu-muli-tang in a rat unpredictable chronic mild stress model
Fitoterapia
(2012) - et al.
Effects of perillaldehyde on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration
Pharmacol. Biochem. Behav.
(2014)