Abstract
Hesperidin, a well-known flavanone glycoside mostly found in citrus fruits, showed neuroprotective and antidepressant activity. Agomelatine, a melatonergic MT1/MT2 agonist and 5-HT2C receptor antagonist, exhibits good antidepressant efficacy. Bupropion has been widely used for the treatment of depression because of its dopamine and norepinephrine reuptake inhibition. The objective of present study was to assess the antidepressant effects of hesperidin combination with agomelatine or bupropion. Male Swiss Albino mice received treatment of saline, vehicle, ‘hesperidin alone', ‘agomelatine alone', hesperidin+agomelatine, ‘bupropion alone', hesperidin+bupropion, and agomelatine+bupropion for 14 days. The immobility period was analysed 30 min after the treatment in forced swim and tail suspension tests. Dopamine and serotonin levels were analysed in hippocampus, cerebral cortex, and whole brain using HPLC with fluorescence detector. Hesperidin plus agomelatine treated group was better in terms of decrease in immobility period and increase in dopamine and serotonin levels when compared to their respective monotherapy treated groups.
Highlights
Depression is a common mental disorder that affects thought, behaviour, feeling, and physical well-being of an individual
The results of the present study demonstrate that combination of hesperidin plus bupropion, hesperidin plus agomelatine, and agomelatine plus bupropion showed antidepressant-like effects in both in vivo and in vitro test models
The antidepressant activity is expressed in terms of immobility period produced due to inescapable condition in forced swim and tail suspension tests, reflecting behavioural despair as seen in human depression [27]
Summary
Depression is a common mental disorder that affects thought, behaviour, feeling, and physical well-being of an individual. Despite introduction of several novel classes of antidepressant drugs, advances in understanding the psychopharmacology, and biomarkers of major depression, only 60%–70% of patients with depression respond to antidepressant therapy Of those who do not respond, 10%–30% exhibit treatmentresistant symptoms with difficulties in occupational and social function, suicidal thought, decline of physical health, and increased health care utilization [2]. Though they have different mechanisms of action, all present antidepressants produce the same final rates of response and remission [3]. Severe and intolerable side effects of available antidepressants and limited success rate (60–70%) of first-line monotherapy drugs have resulted in preference of potentiation or augmentation therapy in treatment for depression [4]
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