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Depression is categorized as one of the most prevalent psychological disorders that affect personal
wellbeing and social life of individuals. Symptoms vary from anhedonia to suicide commitment.
The molecular mechanism behind is the low concentration of neurotransmitters serotonin,
dopamine and norepinephrine in central nervous system. These are primarily responsible for
regulating and alleviating mood. In the chronic mild stress (CMS) model of depression, silymarin,
a plant-derived polyphenolic flavonoid of Silybum marianum, elicited strong antidepressant-like
action. It increased the levels of monoamines, particularly 5-hydroxytryptamine (5-HT) in the
cortex and dopamine (DA) in the mice hippocampal region and prefrontal cortex. The objective of
the current research was to investigate silymarin's antidepressant potential in CMS-induced
depressive-like behavior in mice and to identify its potential mechanism(s) of action. The mice
were given silymarin and silymarin loaded liposomal nanoparticles (SLNPs) for two weeks after
following CMS protocol for 28 days (4 weeks). Animals were assessed for behavioral alterations,
including exploratory activity in an open field test, behavioral despair in a forced swim test, and
anxiety-like behaviors in an elevated plus maze test. There lies a close relationship between
depression and inflammatory liver diseases. Hence the effect of depression on liver has also been
checked. Silymarin is a commercially available hepatoprotective drug but due to its antioxidant
properties, research has been conducted to evaluate its neuroprotective effect and hence its
prescription as antidepressant drug. However, due to its poor solubility and bioavailability there is
delay in the onset of treatment outcomes in many individuals. Certain side effects and
contraindications are also important regimen opponents. In this study, Silymarin loaded liposomal
nanoparticles (SLNPs) are prepared, characterized, and realized for the depression treatment in
Chronic Mild Stress (CMS) mice model of depression and its treatment efficiency on symptoms
of inflammatory liver diseases in mice as well. It presented face construct and validity response.
As such the SLNPs present improvement in depression measurement parameters as compared to
the simple silymarin. The SLNPs also positively impacted the aggression, anhedonia and rearing
in mice, however simple silymarin treated mice did not show improvement in social and personal
behavior. As such SLNPs compensated for delayed onset of fluoxetine response.