The modulatory role of 6-gingerol-rich portion of ginger on brain oxidative stress, inflammation and neurotransmission in chronic unpredicted mild stress-induced depressed male Wistar rats.

Objective: This study was designed to investigate the effect of 6-gingerol-rich extract of ginger (6-GIRPOG) on oxidative stress, inflammation and neurotransmission in chronic unpredicted mild stress (CUMS)-induced depressed male Wistar rats. Materials and Methods: Twenty-five (25) male Wistar rats in total were divided into five groups at random (n = 5 in each group). The control group received 0.5 ml of normal saline, CUMS rats were only exposed to CUMS daily, CUMS + fluoxetine rats were exposed to CUMS and orally received 10 mg/kg per body weight of fluoxetine daily, CUMS + 6-GIRPOG (100) and CUMS + 6-GIRPOG (200) rats were exposed to CUMS and orally received 100 and 200 mg/kg body weight of 6-GIRPOG respectively (daily). Exposure to CUMS and treatment were carried out for a period of 21 days, after which light and dark box test, sucrose splash test, and forced swim test were conducted to assess the behavioral functions. The rats were then euthanized and their brain samples were collected for biochemical analysis. Results: The exposure to CUMS caused behavioral alterations as well as a significant (p<0.05) decrease in the levels of brain-derived neurotrophic factor (BDNF), glutamate, reduced glutathione (GSH), and activities of superoxide dismutase (SOD). Furthermore, the exposure to CUMS caused a statistically significant rise (p<0.05) in the brain norepinephrine, cortisol, nuclear factor kappa-B (NFK-B), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. However, the administration of both 100 and 200 mg/kg of 6-GIRPOG effectively reversed these behavioral and biochemical changes. Conclusion: Consequently, the study reveals the role of 6-GIRPOG in ameliorating CUMS-induced depression and brain damage via antioxidative, anti-inflammatory, and neurotransmission modulatory mechanisms.