Abstract
BackgroundThe majority of patients with chronic fatigue have a risk of comorbidity with depression. Pinocembrin (PB) is a kind of flavonoid molecule isolated from honey and propolis and has antimicrobial, anti-inflammatory, antioxidant, and anticancer function. The purpose of the current study was to determine the possible function of PB on treatment of depression.MethodsA chronic unpredictable mild stress (CUMS) mouse model was established to mimic the depressive-like behaviors in vivo. The depressive-like behaviors of CUMS mice were measured by sucrose preference test (SPT), open field test (OFT), forced swim test (FST) and tail suspension test (TST). The concentration of reactive oxygen species (ROS), malondialdehyde (MDA) and the activity or superoxide dismutase (SOD) were detected by commercial kit. The inflammatory factor including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-10 and transforming growth factor (TGF)-β were examined.ResultsWe found that PB alleviated the decreasing of sucrose preference and body weight. CUMS mice significantly increased the immobility time but decreased latency to abandon in FST, increased the immobility time in TST, and reduced crossing score and rearing score in OFT, whereas these changes were reversed by PB treatment. More importantly, PB decreased the concentration of ROS and MDA, but increased the SOD activity, suggesting that it could protected against oxidative stress in CUMS mice. Interestingly, PB inhibited cell apoptosis and regulated inflammatory factors expression in hippocampus of CUMS mice. Moreover, PB activated Nrf2/HO-1 signal pathway but inhibited the phosphorylation of NF-kB.ConclusionsIn conclusion, PB mitigated CUMS-induced depressive-like behaviors through ameliorating neuroinflammation and apoptosis.Trial registrationNot Applicable.
Highlights
The majority of patients with chronic fatigue have a risk of comorbidity with depression
The release of pro-inflammatory cytokines, especially interleukin-1 cytokines (IL-1) and tumor necrosis factor (TNF-), is higher in depressed patients compared with normal patients, indicating that inflammation plays an vital role in the pathophysiology of depression (AlHakeim et al 2015; Eyre et al 2016; Hannestad et al 2011)
The PB or imipramine hydrochloride (IMI) treatment could alleviate the decreasing of sucrose preference and body weight (Fig. 1B and C)
Summary
The majority of patients with chronic fatigue have a risk of comorbidity with depression. The purpose of the current study was to determine the possible function of PB on treatment of depression. Cerebral oxidative stress is an important mechanism of brain dysfunction, especially depression and anxiety (Tell and Gustincich 2009). The release of pro-inflammatory cytokines, especially interleukin-1 cytokines (IL-1) and tumor necrosis factor (TNF-), is higher in depressed patients compared with normal patients, indicating that inflammation plays an vital role in the pathophysiology of depression (AlHakeim et al 2015; Eyre et al 2016; Hannestad et al 2011). Higher expression of pro-inflammatory cytokines have been identified in depressed animal models (Jiang et al 2017a). These findings suggest that the antiinflammatory and anti-apoptotic functions play vital roles in depression treatment
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