concanavalin-a and thymoquinone

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

Three different concentrations of Nigella sativa (N. sativa) ethanolic extract, thymoquinone (TQ), dexamethasone, and saline were examined to see whether they had any effects on cell viability, proliferation, and interleukin 4 (IL-4) and interferon-γ (IFN-γ) secretion in non-stimulated, phytohemagglutinin (PHA) and concavaline A (Con A)-stimulated splenocytes. In PHA and Con A-stimulated splenocytes, cell viability and proliferation were increased and Con A shifted cytokine profile towards Th2 balance. Dexamethasone treatment showed a suppression in viability, IFNγ and IL-4 secretion in non-stimulated and stimulated splenocytes. Extract and TQ reduced the viability and inhibited the proliferation of stimulated and non-stimulated splenocytes concentration-dependently. Higher concentrations of N. sativa (1000 mg/ml) and TQ (5 and 10 mg/ml) reduced the secretion of IL-4 in stimulated cells. Two higher concentrations of N. sativa had decreased IFNγ secretion in both stimulated and non-stimulated cells. In non-stimulated cells, only the highest and in Con A-stimulated cells, all TQ concentrations had inhibited IFNγ secretion. The highest concentration of N. sativa increased IFNγ/IL-4 ratio in both stimulated and non-stimulated cells while higher concentrations of TQ only had the same effect on stimulated cells. N. sativa and TQ showed cytotoxic inhibitory effect on rat splenocytes and on Th1/Th2 cytokines concentration-dependently. Higher concentrations of extract and TQ increased cytokines balance in Th1/Th2.

Topics: Animals; Benzoquinones; Cell Proliferation; Cell Survival; Cells, Cultured; Concanavalin A; Cytokines; Dexamethasone; Gene Expression Regulation; Male; Nigella sativa; Phytohemagglutinins; Plant Extracts; Rats; Rats, Wistar; Spleen