Hong SC, Du YY, Wang GB, Wang SQ, Zheng YF, Wang N, Situ HL, Wang ZY. Chinese herbal formulas alleviated depression in breast cancer patients: A meta-analysis, network pharmacology and experimental validation. World J Psychiatry 2026; 16(4): 115981 [DOI: 10.5498/wjp.v16.i4.115981]
Corresponding Author of This Article
Zhi-Yu Wang, MD, PhD, Full Professor, Principal Investigator, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, No. 111 Dade Road, Guangzhou 510000, Guangdong Province, China. wangzhiyu@gzucm.edu.cn
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Oncology
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Meta-Analysis
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Apr 19, 2026 (publication date) through Apr 1, 2026
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World Journal of Psychiatry
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Hong SC, Du YY, Wang GB, Wang SQ, Zheng YF, Wang N, Situ HL, Wang ZY. Chinese herbal formulas alleviated depression in breast cancer patients: A meta-analysis, network pharmacology and experimental validation. World J Psychiatry 2026; 16(4): 115981 [DOI: 10.5498/wjp.v16.i4.115981]
World J Psychiatry. Apr 19, 2026; 16(4): 115981 Published online Apr 19, 2026. doi: 10.5498/wjp.v16.i4.115981
Chinese herbal formulas alleviated depression in breast cancer patients: A meta-analysis, network pharmacology and experimental validation
Shi-Cui Hong, Yu-Yi Du, Gui-Bin Wang, Sheng-Qi Wang, Yi-Feng Zheng, Neng Wang, Hong-Lin Situ, Zhi-Yu Wang
Shi-Cui Hong, State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
Yu-Yi Du, Gui-Bin Wang, Sheng-Qi Wang, Yi-Feng Zheng, Hong-Lin Situ, Zhi-Yu Wang, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
Neng Wang, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
Author contributions: Hong SC, Wang N, Situ HL, and Wang ZY contributed to the conception, methodology and interpretation; Hong SC, Du YY, Wang GB, Wang SQ, and Zheng YF contributed to statistical analysis and data collection; Hong SC and Wang ZY contributed to writing.
Supported by National Natural Science Foundation of China, No. 82374446, No. 82174165, and No. 82474512; the State Key Laboratory of Dampness Syndrome of Chinese Medicine, No. SZ2021ZZ19; Science and Technology Planning Project of Guangdong Province, No. 2022B1515230002 and No. 2023B1212060063; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, No. 2020B1212030006; Guangzhou Science and Technology Project, No. 2025CX009 and No. 2023A03J0236; Guangdong Traditional Chinese Medicine Bureau Project, No. 20231143; and the Specific Research Fund for CHF Science and Technology of Guangdong Provincial Hospital of Chinese Medicine, No. YN2023MS31.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Zhi-Yu Wang, MD, PhD, Full Professor, Principal Investigator, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, No. 111 Dade Road, Guangzhou 510000, Guangdong Province, China. wangzhiyu@gzucm.edu.cn
Received: October 31, 2025 Revised: December 16, 2025 Accepted: January 15, 2026 Published online: April 19, 2026 Processing time: 151 Days and 1.4 Hours
Abstract
BACKGROUND
Depression represents a frequent comorbidity in breast cancer patients. However, many antidepressants have a certain degree of adverse reactions and decline patients’ compliance to conventional therapies. Chinese herbal formulas (CHF), with its long-standing application in mood disorders, offers a potential alternative. Nevertheless, comprehensive evidence regarding its effectiveness specifically for depression in breast cancer populations remains limited.
AIM
To systematically evaluate the efficacy of CHF interventions for depression in breast cancer patients and explore the potential mechanisms.
METHODS
We systematically searched four English databases (PubMed, EMBASE, the Cochrane Library, PsycINFO) and four Chinese databases (CNKI, CBM, VIP, Wanfang) from their inception through June 2024. The investigation focused on CHF’s effects on psychological outcomes [depression and quality of life (QOL)], neurochemical parameters (serotonin, norepinephrine, and dopamine levels) and immunological indicators (CD4+ and CD8+ T lymphocyte counts). Network pharmacology and experimental analysis of clinical samples were employed to elucidate the mechanisms of the core formula Si-Ni-San (SNS).
RESULTS
Pooled data from 20 randomized trials (n = 1607) demonstrated CHF’s superiority over antidepressants in reducing Hamilton Depression Rating Scale scores (mean difference = -5.33, 95% confidence interval: -6.93 to -3.73, P < 0.05) and enhancing QOL (mean difference = 9.13, 95% confidence interval: 6.69-11.57, P < 0.05). CHF significantly elevated monoamine neurotransmitter levels (all P < 0.05) and CD4+ T cell counts (P < 0.05), with no effect on CD8+ subsets. Subgroup analysis revealed enhanced efficacy with interventions ≥ 4 weeks. Safety profiles favored CHF, with fewer adverse events vs antidepressants. Network pharmacology analysis suggested that SNS may exert its effects by modulating immune responses and serotonergic synapse pathways. Experimental analysis of clinical samples further indicated that the antidepressant effects of SNS may be mediated through the regulation of CD4+ T cells and rebalancing of neurotransmitter, tryptophan metabolism.
CONCLUSION
This systematic review establishes CHF as an effective and safe intervention for depression in breast cancer patients, with benefits extending to QOL, monoamine neurotransmitter levels and immunological parameters. Moreover, SNS represents a promising complementary therapy with multi-pathway mechanisms of action, particularly involving immune and metabolic pathways.
Core Tip: In present study, we found that Chinese herbal formulas outperformed antidepressants in reducing depression and improving quality of life, significantly elevated monoamine neurotransmitter levels, and selectively increased CD4+ T-cell counts. Network pharmacology revealed that Si-Ni-San may modulate immune responses and serotonergic synapses, while experimental validation indicated involvement of CD4+ T cells and rebalancing of neurotransmitter, tryptophan metabolism. These results advocate for the integration of Chinese herbal formulas especially Si-Ni-San into integrative care protocols for breast cancer-related depression and underscore the need for further mechanistic and clinical investigation.
