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World J Psychiatry. Jun 19, 2026; 16(6): 114553
Published online Jun 19, 2026. doi: 10.5498/wjp.v16.i6.114553
Published online Jun 19, 2026. doi: 10.5498/wjp.v16.i6.114553
Exploring the antidepressant mechanisms of Guipi pill: A focus on gut-brain axis and immunity modulation
Jing Zhong, Wei Chen, Sen Li, Jia-Hui Huang, Department of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Dong-Lin Zheng, Department of Gastroenterology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
Yi-Dan Wang, Department of Basic Science, Guangxi University of Chinese Medicine, Nanning 541100, Guangxi Zhuang Autonomous Region, China
Xing-Qiu Liang, Department of Science and Technology, Ruikang Hospital Affiliated to Gua
Ming-Kun Liang, Traditional Chinese Medicine Specialty Office, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 541100, Guangxi Zhuang Autonomous Re
Co-first authors: Jing Zhong and Wei Chen.
Co-corresponding authors: Xing-Qiu Liang and Ming-Kun Liang.
Author contributions: Zhong J, Chen W, Li S, Zheng DL, Wang YD, and Huang JH contributed to investigation; Zhong J and Chen W were responsible for conceptualization, methodology, and writing-draft, they contributed equally to this article, they are the co-first authors of this manuscript; Li S handled software-related work; Liang XQ and Liang MK provided conceptualization, supervision, and writing review and editing, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors have read and approved the final manuscript.
AI contribution statement: Only DeepL was used for language polishing in manuscript revision; ChatGPT and Grammarly were not employed. All core scientific content, including study design, data analysis, results interpretation, and figures, was independently created by the authors without AI involvement. No AI-generated images were included, and all charts were manually produced using professional tools.
Supported by National Natural Science Foundation of China, No. 81960807; Guangxi Natural Science Foundation, No. 2023GXNSFAA026237; Guangxi Xinglin Young Talents Project of Guangxi University of Traditional Chinese Medicine, No. 2022C026 and No. 2022C042; and Guangxi Zhuang Autonomous Region’s First Batch of Medical Young Reserve Talent Training Program.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Guangxi University of Traditional Chinese Medicine.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Xing-Qiu Liang, PhD, Department of Science and Technology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, No. 10 Huadong Road, Nan
Received: September 23, 2025
Revised: November 14, 2025
Accepted: February 2, 2026
Published online: June 19, 2026
Processing time: 248 Days and 0.1 Hours
Revised: November 14, 2025
Accepted: February 2, 2026
Published online: June 19, 2026
Processing time: 248 Days and 0.1 Hours
Core Tip
Core Tip: This study demonstrates that the traditional formula Guipi pill (GPP) alleviates depression by modulating the gut-brain axis via immune regulation. GPP significantly improved depressive-like behaviors in a chronic unpredictable mild stress rat model and altered the expression of 1349 genes, with GZMA playing a key role. Mechanistically, GPP enhanced GZMA expression in CD8+ T-cell subsets, promoting effector T cells while reducing naïve T cells. These results suggest a novel immune-mediated pathway for GPP’s antidepressant effect.