Antidepressant effect of Crossopteryx febrifuga trunk bark aqueous extract on chronic stress-induced depression-related behaviors in male and female rats

Depression is a highly prevalent neuropsychiatric disorder globally, and its increasing incidence is thought to be mediated by the growing exposure to stressful life events and conditions. Crossopteryx febrifuga is widely used in traditional medicine to treat fever, pain, epilepsy, and depression. This study aimed at evaluating the antidepressant effect of C. febrifuga aqueous extract (CF) using the chronic physical restriction stress (CRS) model on male and female rats. Sixty Wistar rats were randomly divided into six groups of 10 rats each (5 males and 5 females per group) were used. CRS was used to induce depressive-like behavior in rats for a period of 21 days. Novelty-suppressed feeding test (NSFT) and the forced swimming test (FST) were used to delineate depressive behavior. Corticosterone, serotonin, dopamine, noradrenalin, MAO, BDNF, and cytokines (IL-1, IL-6, IL-10, TNF-α), as well as oxidative and nitrosative stress markers such as NO, MDA, SOD, GSH, and CAT expressions, were evaluated. Histological sections of hippocampi were achieved to verify structural changes in neural architecture. From the results, in the negative control group both in female and male, CRS induced an increment in the time taken to consume food associated with a decrement in the quantity of food consumed in NSFT, an increase in immobility time, and a decrease in climbing and swimming times in the FST. CF reversed these different parameters in both male and female rats compared to the negative control group. All CF doses also led to a decrease in corticosterone and MAO concentrations and an increase in serotonin, dopamine, and noradrenaline concentrations. CF decreased the concentration of MDA and NO, increased GSH concentration (only in females, with all extract doses), and SOD and CAT activity (only in females at 25 mg/kg). All CF doses also affected cytokine expression by decreasing IL-1, IL-6, and TNF-α concentrations, associated with an increase of IL-10 in female subjects only. CF protected hippocampal structures and amygdala in both males and females. After 21 days, CRS induced a depressed state in rats of the negative control group. However, CF shown and antidepressant effect both in female and male by reversed all these trends on corticosolaemia, thus modulating monoamine concentrations, oxidative status, and through anti-inflammatory and anti-acetylcholinesterase actions. These effects could be attributed to their polyphenols, flavonoids, saponins, and tannins-rich content.