Baicalein Protects against Repeated Unpredictable Stress-Induced Depression-like Behavior in Mice

Abstract Baicalein, an active flavonoid derived from the root of Scutellaria baicalensis, has been extensively utilized in the treatment of stress-related neuropsychiatric disorders, encompassing behaviors indicative of depression and anxiety. The precise neurochemical and molecular biological mechanisms underlying the effect of baicalein on depression-like behavior have yet to be elucidated. In the current study, mice were administered baicalein at dosages of 10, 20, or 40 mg/kg (intraperitoneally) 30 minutes before being subjected to daily exposure to unpredictable stress over a period of 14 days. The tail suspension test and the forced swimming test, along with the novelty suppressed feeding test and the sucrose preference test, were employed to assess the protective effects of baicalein against depression- and anxiety-like behaviors induced by chronic stress. The outcomes indicated that baicalein notably reduced the duration of immobility in both the forced swimming test and tail suspension test, elevated sucrose consumption, and diminished the latency to feed, thereby reflecting its antidepressant and anxiolytic properties. Additionally, baicalein elevated the concentrations of serotonin and dopamine and suppressed monoamine oxidase activity within the hippocampus and cortex of stressed mice. Following baicalein treatment, the levels of cyclic adenosine monophosphate and the messenger RNA expression of the brain-derived neurotrophic factor were also observed to increase in these brain regions. These results suggest that baicalein may safeguard mice from depression- and anxiety-like behaviors precipitated by chronic stress, potentially through the augmentation of monoamine levels by inhibiting monoamine oxidase activity, and by stimulating the production of cyclic adenosine monophosphate and brain-derived neurotrophic factor in brain areas implicated in emotional disorders. Baicalein could prove to be a significant agent for the prevention or mitigation of the multifaceted symptoms associated with depression and anxiety.