Protective Effects of Silibinin and Its Possible Mechanism of Action in Mice Exposed to Chronic Unpredictable Mild Stress

Abstract

Silibinin, a natural flavonoid antioxidant isolated from extracts of the milk thistle herb, has recently been identified as having anti-hepatotoxic and anticancer properties. In this paper, we investigated the effects of silibinin on behavior and neuroplasticity in mice subjected to chronic unpredictable mild stress (CUMS). After 5 consecutive weeks of CUMS, the mice were treated with silibinin (100 mg/kg, 200 mg/kg and 400 mg/kg by oral gavage) for 3 consecutive weeks. The results showed that silibinin administration significantly alleviated the CUMS-induced depressive-like behavior, including the total number of squares crossed and the frequency of rearing in the open field test, the immobility time in the tail suspension test and the forced swimming test. Furthermore, silibinin treatment increased the levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT) and norepinephrine (NE) in the prefrontal cortex and hippocampus. Our study provides new insight into the protective effects of silibinin on the depressive status of CUMS mice, specifically by improving neuroplasticity and neurotransmission.

Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7

“…When the depressed animals showed an increase in immobility time in the TST, they did not produce locomotion changes in the OFT (Millon et al, 2015, Pazini et al, 2015. However, in a number of reports, depressed rodents showed behavioral despair in the TST and decreased locomotor activity in the OFT (Ge et al, 2014, Demuyser et al, 2015, Niu et al, 2015, Yan et al, 2015. The decreased number of crossings or distance moved in 5 min mainly reflected the emotional profile of depressed animals instead of impaired locomotor activity because that the locomotor activity in a long time (30 min) did not changed (Demuyser et al, 2015).…”

“…In rodents, the sucrose preference and tail suspension test were used to assess the prominent symptom of depression, anhedonia (Der-Avakian and Markou, 2012) and despair behavior (Cryan et al, 2005, Ge et al, 2014 respectively. The open field test was employed to determine the emotional profile of rats, in which locomotor activity, exploratory behavior and measures of anxiety were observed (Campos et al, 2013), and also frequently used in the behavior studies in depressed rodents (Ge et al, 2014, Boyko et al, 2015, Yan et al, 2015. Locomotor measure in the OFT was used to investigate a possible bias on the effects observed in the TST.…”

Cytisine, a Partial Agonist of α4β2 Nicotinic Acetylcholine Receptors, Reduced Unpredictable Chronic Mild Stress-Induced Depression-Like Behaviors

“…Levels of BDNF is decreased in depression disorders ( Yan et al ., 2015 ). UCMS decreased the expression levels of BDNF in hippocampus and amygdala of UCMS mice, whereas treatment of CYT increased the BDNF levels in the hippocampus and amygdala (Hippocampus: F (2, 15) =25.798, p <0.001, LSD test; Fig.…”

“…Brain-derived neurotrophic factor (BDNF) functions in both the peripheral and central nervous systems (CNS) and has a beneficial impact on supporting the survival of existing neurons and promoting the growth of newly differentiated neurons and synapses ( Bergami and Berninger, 2012 ). Several lines of evidence indicate that chronic stress and low level of BNDF are the key components of depression pathology ( Yan et al ., 2015 ).…”

Up-Regulation of αCaMKII Impairs Cued Fear Extinction and NMDAR-Dependent LTD in the Lateral Amygdala

“…As described previously (Yan et al, 2015), briefly, each mouse was placed in an acrylic open-field chamber (27 cm long × 27 cm wide × 38 cm high) for 30 min. The amount of moving distance, the time in the center area, and the number of rearing were measured using a Tru-scan DigBahv-locomotion Activity Video Analysis System (Coulbourn Instruments, USA).…”