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

doi:10.5498/wjp.v15.i10.101658

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World Journal of Psychiatry

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2220-3206

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Randomized Controlled Trial

World J Psychiatry. Oct 19, 2025; 15(10): 101658
Published online Oct 19, 2025. doi: 10.5498/wjp.v15.i10.101658

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

Dian-Ming Zhu, Ying Lu, Xu-Dong Xiao, Yang Sun, Gang Tao, Bin Long, Jing Zhao

Dian-Ming Zhu, Ying Lu, Xu-Dong Xiao, Yang Sun, Bin Long, Jing Zhao, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Traditional Chinese Medicine for Mental Health, Shanghai 201108, China

Gang Tao, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang 212008, Jiangsu Province, China

Co-first authors: Dian-Ming Zhu and Ying Lu.

Co-corresponding authors: Bin Long and Jing Zhao.

Author contributions: Zhu DM and Lu Y contributed equally to this work and are considered co-first authors; Zhu DM, Lu Y, and Xiao XD were responsible for data collection, clinical assessments, and statistical analysis; Sun Y participated in the patient recruitment and follow-up; Tao G provided clinical guidance and supervised the study implementation at the Zhenjiang site; Long B and Zhao J conceived and designed the study, performed the network pharmacology analysis, and revised the manuscript; All authors read and approved the final manuscript.

Institutional review board statement: All study procedures and protocols were approved by Shanghai Mental Health Center’s Ethics Committee (No. 2021-17).

Clinical trial registration statement: This study is registered at the Clinical Trial Registry of the Ethics Committee of Zhenjiang Hospital of Traditional Chinese Medicine. The registration identification number is No. ChiCTR2100049259.

Informed consent statement: Signed informed consents by the patient or their legal guardian have been provided.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Jing Zhao, MD, Doctor, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Traditional Chinese Medicine for Mental Health, No. 3210 Humin Road, Minhang District, Shanghai 201108, China. maggy-1978@163.com

Received: September 22, 2024
Revised: April 10, 2025
Accepted: August 7, 2025
Published online: October 19, 2025
Processing time: 368 Days and 18.7 Hours

Abstract

BACKGROUND

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.

AIM

To evaluate the therapeutic efficacy and underlying mechanisms of Yueju pill combined with olanzapine in treating schizophrenia.

METHODS

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.

RESULTS

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.

CONCLUSION

Yueju pill, when combined with olanzapine, significantly improves clinical outcomes in schizophrenia patients, with safety comparable to olanzapine alone.

Keywords: Schizophrenia; Yueju pill; Olanzapine; Quercetin; Dopamine pathway; Network pharmacology; Brain-derived neurotrophic factor; Cognitive function

Core Tip: This study is the first to report the mechanism of Yueju pill combined with olanzapine in the treatment of schizophrenia. This study finds that Yueju pill combined with olanzapine does not increase adverse effects in the treatment of schizophrenia, demonstrating its safety. This study reveals the association between the upregulation of serum brain-derived neurotrophic factor, dopamine (DA), and serotonin levels and the therapeutic effects of Yueju pill combined with olanzapine in treating schizophrenia. This study preliminarily elucidates the therapeutic targets of Yueju pill through network pharmacology. This study identifies key genes related to the DA pathway, providing new theoretical foundations and molecular targets for the diagnosis and treatment of schizophrenia.