Diosgenin reverses posttraumatic stress disorder in mice by augmenting neurochemical release and inhibiting HPA axis dysfunction, oxidative stress, and neuroinflammation

Abstract

Post-traumatic stress disorder (PTSD) is a mental disorder linked to neurochemical, hypothalamic-pituitary-adrenal (HPA)-axis dysregulations, inflammatory and pro-oxidant challenges in response to traumatic events. It is one of the leading causes of neurocognitive declines, hence prompting the need for a pharmacological intervention. However, the impact of diosgenin, a naturally occurring steroidal saponin with adaptogenic-like action, on PTSD-induced neuropsychiatric disturbances and its underlying mechanisms are unknown. In this study, we investigated the outcome of diosgenin treatment in a multimodal traumatic, single prolonged stress (SPS)-induced PTSD in mice. Following the SPS-induced 7 days of PTSD, mice (n = 9) were thereafter treated with diosgenin (25 and 50 mg/kg) or fluoxetine (10 mg/kg) orally from days 8–20 (14 days). Locomotory, cognitive-, depressive- and anxiety-like behaviors were investigated. We assayed for changes in adrenal weight, serum glucose and corticosterone concentrations. Neurochemical, inflammatory, oxido-nitrergic dysfunctions and monoamine oxidase-B and acetylcholinesterase activities, were measured in the striatum, prefrontal-cortex and hippocampus. The results revealed that the SPS challenge inhibited locomotor, spatial/non-spatial memory functions, increased anxiety and depressive-like features, which were reversed by diosgenin. Diosgenin reduced SPS-induced increased monoamine oxidase-B, acetylcholinesterase activities, TNF-α, IL-6, malondialdehyde and nitrite levels in the striatum, prefrontal-cortex and hippocampus. Antioxidants such as glutathione, superoxide-dismutase, and catalase levels in SPS-mice brains were increased by diosgenin. Moreover, diosgenin attenuated SPS-induced hyper-HPA-axis mediation of PTSD by decreasing serum corticosterone, glucose levels and adrenal gland hypertrophy. Herewith, we suggest that diosgenin convenes adaptogenic-like protection against mice exposed to PTSD by enhancing antioxidant machinery, neurochemical modulations, and inhibition of oxido-nitrergic, inflammatory, and HPA-axis dysfunctions.