Silibinin prevents depression-like behaviors in a single prolonged stress rat model: the possible role of serotonin

Background: Post-traumatic stress disorder (PTSD) is an extreme mood disorder that occurs after experiencing extreme stress, and patients with this disorder are known to accompany with symptoms of depression, anxiety, and memory impairments. Silibinin (SIL) is a natural polyphenolic flavonoid and is the main active ingredient of silymarin, which is primarily extracted from the milk thistle. Although some studies have assessed the properties of this flavonoid, the potential of SIL as a treatment for PTSD patients and its mechanisms of action have yet to be fully elucidated. Methods: After exposure to a model of single prolonged stress (SPS), the open field test (OFT) and forced swimming test (FST), were used to investigate the effects of SIL on anxiety- and depression-like symptoms in male rats. The rats received of SIL (25, 50, and 100 mg/kg) for 14 days following exposure to SPS. Results: Administration of SIL significantly improved anxiety-like behaviors in the OFT, depression-like behaviors in the FST, and freezing behavior in fear conditioning test. SIL also increased levels of serotonin in the hippocampus (Hipp) and amygdala, and enhanced expression of tryptophan hydroxylase-1 mRNA in the Hipp. The administration of SIL also inhibited SPS-induced decreases dopamine levels and increases norepinephrine levels in the Hipp. Conclusions: Taken together, the present findings suggest that SIL can be a useful therapeutic ingredient for the treatment of trauma stress-associated symptoms, including PTSD-induced anxiety and depression caused by PTSD.