IN-VIVO EVALUATION OF SILYMARIN ENCAPSULATED LIPOSOMAL NANOPARTICLES IN CHRONIC MILD STRESS (CMS) MODEL AND DEPRESSION INDUCED LIVER DISORDERS

Abstract

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.