Overweight and obesity are complicated metabolic disorders associated with negative impacts on the brain and its function, including cognitive and memory abilities. Herbal medicines are plant-based bioactive compounds produced by plants. Natural food components with antioxidant activity show promise as alternative treatments for a number of illnesses, including brain diseases. Thymoquinone (TQ) is the main bioactive constituent of essential oils produced from Nigella sativa seeds. TQ possesses numerous biological and pharmacological activities, including antioxidant, anti-inflammatory, antihyperglycemic, and immunomodulatory effects, with neuroprotective effects against various neurodegenerative diseases and pathological conditions of the brain. Several studies have investigated the pharmacological activities of TQ; however, its neuroprotective molecular signaling pathways have not been fully described, and several issues remain to be clarified. The current review summarizes the most recent information related to the important molecular signaling pathways by which TQ protects brain function, particularly in overweight/obese individuals. In conclusion, TQ improved the activity of antioxidant enzymes, maintained redox equilibrium and decreased neuroinflammation and apoptosis via various signaling pathways. Numerous proteins, including nuclear factor erythroid 2–related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), and mitogen-activated protein kinase (MAPK), are crucial for the TQ signaling pathway to prevent brain problems. Although these proteins represent a novel treatment approach, there are still issues with their clinical applicability in various diseases. Researchers should perform further research to determine the additional activity of TQ for the development of clear strategies for the prevention and treatment of brain dysfunction.
Mostafa et al. (2026) studied this question.