Enhancing schizophrenia treatment efficacy: The combined impact of Yueju pill and olanzapine through quercetin target modulation.

Schizophrenia is a complex psychiatric disorder with significant functional impairment. Although olanzapine is effective in treating positive symptoms, its efficacy against negative symptoms and cognitive deficits is limited. Yueju pill, a traditional Chinese herbal formula, has shown potential in improving these domains, but its mechanisms remain largely unexplored. To evaluate the therapeutic efficacy and underlying mechanisms of Yueju pill combined with olanzapine in treating schizophrenia. Ninety-seven patients with schizophrenia were randomly assigned to an intervention group (n = 48) receiving olanzapine and Yueju pill, or a control group (n = 49) receiving olanzapine and a placebo for 8 weeks. Symptom severity was assessed using the positive and negative syndrome scale, the scale for the assessment of negative symptoms, and cognitive and social function scales. Serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), and serotonin (5-HT) were measured. Network pharmacology analysis identified key chemical components and target genes involved in the treatment response. The intervention group demonstrated a significantly higher overall efficacy rate (93.75%) compared to the control group (73.47%, P < 0.05). Improvements in psychiatric symptoms, cognitive function, and social performance were more pronounced in the intervention group. Additionally, serum levels of BDNF, DA, and 5-HT were significantly higher in the intervention group (P < 0.05). Network pharmacology analysis revealed quercetin as a key component, modulating genes such as CHRM1, GSK3B, and KCNH2, crucial in DA signaling. Yueju pill, when combined with olanzapine, significantly improves clinical outcomes in schizophrenia patients, with safety comparable to olanzapine alone.