concanavalin-a and Depressive-Disorder--Major

Global health estimates indicated approximately 322 million people living with depression. Rising cost of depressive illness treatment and non-responsiveness to existing therapies demand continued research to explore new and more potent therapies. Exploring the potential of natural compounds for their potent antidepressant potentials is becoming topic of interest for scientists. Anti-inflammatory activity of thymoquinone, the active ingredient of Nigella sativa, has been well documented. Current study tested thymoquinone for its antidepressant effect in a Concanavalin A (Con A)-induced depressive-like behavior in BALB/c mice. Thymoquinone successfully protected against Con A-induced behavioral despair and anxiety-like behavior. Reduced grooming behavior as a function of Con A treatment, was also reinstated. Underlying mechanism responsible for antidepressant activity of thymoquinone was analyzed by molecular docking. Thymoquinone interacts in halogen-binding pocket (HBP) of serotonin reuptake transporter indicating its potential as serotonin reuptake inhibitor. Results of current study anticipate thymoquinone as a potential antidepressant drug candidate. PRACTICAL APPLICATIONS: Black seeds of Nigella sativa are consumed with traditional and religious reference since centuries. Thymoquinone, active, and abundant component of Nigella sativa, has shown positive effects in multiple studies against arthritis, asthma, hepatic injury, neurodegeneration, and cancer owing to its immunomodulatory and anti-inflammatory attributes. Considering inflammation as one of central components involved in pathophysiology of major depressive disorder, thymoquinone has been evaluated in current study for its antidepressant potential. Positive results of current study propose thymoquinone as an affordable, natural antidepressant drug candidate with better safety profile than currently available antidepressant regimes. Thymoquinone might provide benefits against inflammation-related sickness behavior that is associated with poorer outcome of clinical depression, thus, paving the way for effective drug development against treatment-resistant depression.

Topics: Animals; Benzoquinones; Concanavalin A; Depressive Disorder, Major; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Plant Extracts

Serotonin receptors are present in lymphocytes and might be related to the functionality of these cells in health and in pathology. The serotonergic system is affected in the brain and in peripheral immune cells of depressed patients. The objectives of this work were to evaluate the basal proliferation of lymphocytes, the response to the mitogen concanavalin A, and the role of serotonin 5-HT(1A) receptors. Twenty-nine patients, 19-52 years old, were diagnosed for a major depression episode with the Statistical and Diagnostic Manual-IV of the American Psychiatric Association, approved by ethic committees and gave written consent. The Hamilton depression score was 30.60 +/- 2.65. An apparently healthy group without a family history of psychiatric illness was included. Blood peripheral lymphocytes were isolated by density gradients with Ficoll/Hypaque and differential adhesion to plastic, cultured in 96-well plaques with RPMI-1640 medium with or without 4 mug/ml of concanavalin A. 8-Hydroxy-2-(di-n-propylamino)tetralin (5-40 nM) and WAY-100,478 (0.1-100 microM), agonist and antagonist of 5-HT(1A) receptors, serotonin (12.5-100 nM) or imipramine (0.1-100 microM) were also added. Proliferation was evaluated at 72 h with 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide, and the optical density was 570 nm. Basal proliferation was three times higher in depressed patients than in controls, whereas no response to mitogen was obtained, and 5-HT(1A) receptors significantly reacted to the agonist, with increases of about 31-54% at 10, 20 and 40 nM of the specific agonist, indicating initial activation probably in relation to autoimmunity and overreactivity of these receptors in depression. The antagonist reduced proliferation in mitogen-stimulated lymphocytes, 50% in controls and 70% in depressed patients, with a differential concentration dependency; probably, these receptors are more sensitive in depression due to increased 5-HT(1A) receptor transduction. The antagonist also reduced the stimulation produced by the 5-HT(1A) agonist. Imipramine caused biphasic effects according to concentrations, showing a possible dual role for serotonin, although all values were significantly higher in depressed subjects. The described alterations might be of relevance in the pathophysiology of depression.

Topics: Adult; Antidepressive Agents, Tricyclic; Cell Proliferation; Concanavalin A; Depressive Disorder, Major; Female; Humans; Imipramine; Lymphocytes; Male; Middle Aged; Mitogens; Receptors, Serotonin, 5-HT1; Serotonin; Serotonin Agents