J Food Biochem. 2020;00:e13348. wileyonlinelibrary.com/journal/jfbc | 1 of 11 https://doi.org/10.1111/jc.13348 © 2020 Wiley Periodicals LLC Received: 3 February 2020 | Revised: 14 May 2020 | Accepted: 27 May 2020 DOI: 10.1111/jfbc.13348 FULL ARTICLE Thymoquinone harbors protection against Concanavalin A-induced behavior deficit in BALB/c mice model Sadia Nazir 1 | Rai Khalid Farooq 2 | Hina Khan 1 | Tahseen Alam 1 | Aneela Javed 1 1 Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan 2 Department of Neuroscience Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia Correspondence Aneela Javed, Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST), H-12 Campus, Islamabad, Pakistan. Email: javedaneela19@gmail.com Abstract Global health estimates indicated approximately 322 million people living with de- pression. Rising cost of depressive illness treatment and non-responsiveness to exist- ing therapies demand continued research to explore new and more potent therapies. Exploring the potential of natural compounds for their potent antidepressant poten- tials is becoming topic of interest for scientists. Anti-inflammatory activity of thymo- quinone, 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 pro- tected 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 inhibi- tor. 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-inflamma- tory 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 pro- pose 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 associ- ated with poorer outcome of clinical depression, thus, paving the way for effective drug development against treatment-resistant depression. KEYWORDS antidepressant, anxiety, Concanavalin A, sickness behavior, thymoquinone