The effects and mechanisms of baicalin on MK-801 induced schizophrenia model mice

Abstract

Background

Schizophrenia (SCZ) pharmacotherapy relies on Western medications with limited efficacy/significant adverse effects. Baicalin (BA), a purified botanical monomer, shows promise as a safer multitarget antipsychotic candidate.

Objective

To study the effect and mechanism of Baicalin on MK-801 induced schizophrenia model mice.

Methods

Behavioral assessments (water maze, open field, dark avoidance, forced swimming tests) evaluated emotional/cognitive functions in MK-801 induced schizophrenia mice. Histological staining analyzed hippocampal, prefrontal cortical, and striatal morphology. Serum inflammatory markers (NF-κB, IL-6, IL-1β, TNF-α) and oxidative stress indicators (SOD, MDA) were quantified by ELISA, alongside hippocampal neurotransmitter levels (DA, 5-HT, GABA, AChE). This study employed a network pharmacology approach to screen the mechanisms of action of baicalin in the treatment of schizophrenia. Western blotting determined hippocampal PI3K/Akt/GSK3β pathway protein expression.

Results

Network pharmacology analysis revealed that baicalin may exert its therapeutic effects in the treatment of schizophrenia through modulation of the PI3K-Akt signaling pathway. Versus model group, BA doses significantly decreased: IL-1β, IL-6, GABA, AChE, MDA, TNF-α, NF-κB; open field total distance; forced swimming immobility; dark avoidance errors (p < 0.05). Increased: DA, 5-HT; water maze platform crossings; dark avoidance latency (p < 0.05). Staining confirmed BA reduced cerebral oxidative stress/neuroinflammation. Western blot showed dose-dependent elevation of p-Akt/Akt and p-GSK3β/GSK3β ratios.

Conclusion

Baicalin may improve cognitive impairments in MK801-induced schizophrenia model mice through the PI3K/Akt/GSK3β signaling pathway, exhibiting anti-neuroinflammatory and neuroprotective effects.