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

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- κ B, IL-6, IL-1 β , 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/GSK3 β 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-1 β , IL-6, GABA, AChE, MDA, TNF- α , NF- κ B; 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-GSK3 β /GSK3 β ratios. Conclusion Baicalin may improve cognitive impairments in MK801-induced schizophrenia model mice through the PI3K/Akt/GSK3 β signaling pathway, exhibiting anti-neuroinflammatory and neuroprotective effects.