Silibinin Alleviates Cognitive Dysfunction, Biochemical Alterations, and Hippocampal Structural Changes Induced by 5 days of Sleep Deprivation with or Without a Subsequent 24-H Recovery in Rats.

Sleep deprivation (SD) impairs cognitive function through oxidative stress, neuroinflammation, and neuroendocrine dysregulation, whereas recovery sleep may not fully reverse these alterations. Silibinin possesses antioxidant, anti-inflammatory, and neuroprotective properties; however, its potential to facilitate recovery following prolonged SD remains unclear. This study investigated the effects of silibinin on cognitive dysfunction and hippocampal alterations induced by 5 days of SD, with or without a subsequent 24-h recovery period, in rats. Forty-eight adult male rats were allocated to control (n = 16), SD (n = 8), SD + recovery (n = 8), SD + silibinin (n = 8), and SD + silibinin + recovery (n = 8) groups. Cognitive performance was assessed using the Open Field Test, Morris Water Maze, and Y-Maze. Serum oxidative stress (MDA and SOD), inflammatory (TNF-α and IL-6), and hormonal biomarkers were evaluated. Hippocampal BDNF and CaMKII levels, histopathological changes, and the immunohistochemical expression of PCNA, synaptophysin, and GFAP were also assessed. SD significantly impaired cognitive performance (P < 0.05), increased oxidative stress and inflammatory cytokines (P < 0.01), altered stress-related hormones (P < 0.05), decreased hippocampal BDNF and CaMKII levels (P < 0.001) and induced marked histopathological and immunohistochemical changes. A 24-h recovery period partially ameliorated these alterations. Silibinin treatment significantly attenuated the SD-induced behavioral, biochemical, hormonal, histopathological, and immunohistochemical alterations (P < 0.05), with further improvement following recovery sleep (P < 0.05), restoring most parameters to levels comparable to those of the control group. These findings suggest that silibinin protects against SD-induced cognitive dysfunction and hippocampal injury by attenuating oxidative stress, neuroinflammation, and neuroendocrine disturbances while enhancing recovery during subsequent recovery sleep.