Li RT, Lan BJ, Xiao ZY, Shi QH, Chen XY, Li F. Sini-Suanzaoren decoction regulates mitochondrial biogenesis mediated by MT-SIRT1 in the treatment of insomnia rats. World J Psychiatry 2025; 15(12): 108867 [PMID: 41357936 DOI: 10.5498/wjp.v15.i12.108867]
Corresponding Author of This Article
Feng Li, PhD, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring East Road, Chaoyang District, Beijing 102488, China. lifeng_bucm0610@126.com
Research Domain of This Article
Psychology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Dec 19, 2025 (publication date) through Dec 9, 2025
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Journal Information of This Article
Publication Name
World Journal of Psychiatry
ISSN
2220-3206
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Li RT, Lan BJ, Xiao ZY, Shi QH, Chen XY, Li F. Sini-Suanzaoren decoction regulates mitochondrial biogenesis mediated by MT-SIRT1 in the treatment of insomnia rats. World J Psychiatry 2025; 15(12): 108867 [PMID: 41357936 DOI: 10.5498/wjp.v15.i12.108867]
Ru-Ting Li, Bi-Juan Lan, Zhuo-Yang Xiao, Qing-Huan Shi, Xin-Yi Chen, Feng Li, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
Author contributions: Li RT initiated the project, designed the experiment and conducted data collection; Li RT, Lan BJ, Shi QH and Chen XY participated in animal experimentation; Li RT and Xiao ZY conducted the collation and statistical analysis, and wrote the original manuscript; Li F make critical revisions to important knowledge content; all authors read and approved the final manuscript.
Supported by the Beijing Natural Science Foundation, No. 7232289.
Institutional animal care and use committee statement: The study was approved by the Animal Ethics Committee of Beijing University of Chinese Medicine (No. BUCM-2024050806-2107).
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: All data generated or analyzed during this study are included in this published article.
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: Feng Li, PhD, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring East Road, Chaoyang District, Beijing 102488, China. lifeng_bucm0610@126.com
Received: July 1, 2025 Revised: August 6, 2025 Accepted: September 19, 2025 Published online: December 19, 2025 Processing time: 149 Days and 1.4 Hours
Abstract
BACKGROUND
Insomnia is closely associated with anxiety and depression, with its pathogenesis involving biological, psychological, and social factors. Sini powder and Suanzaoren decoction are clinically effective traditional Chinese medicine formulas for insomnia, demonstrating promising bioactivity. However, the capability of the active components of Sini-Suanzaoren decoction (SNSZRD) to cross the blood-brain barrier (BBB) and their precise molecular mechanisms, particularly concerning the MT-SIRT1 pathway and mitochondrial function, remain largely unexplored.
AIM
To elucidate the bioactive components of SNSZRD that are capable of BBB penetration and investigate the therapeutic mechanism of SNSZRD against insomnia.
METHODS
The chemical components of SNSZRD were analyzed through liquid chromatography-mass spectrometry (LC-MS). Male Sprague-Dawley rats were intraperitoneally injected with DL-4-chlorophenylalanine (PCPA) to establish an insomnia model. Rats were divided into control, model, eszopiclone (positive control), and SNSZRD low-/medium-/high-dose groups. Molecular docking predicted BBB-penetrating components and their binding affinity for SIRT1. Key pathways were analyzed through open-field tests, elevated plus-maze tests, pentobarbital-induced sleep experiments, Haematoxylin and eosin staining, Nissl staining, ELISA, Western blot analysis, quantitative real-time PCR, and immunohistochemistry.
RESULTS
LC-MS identified 1574 compounds in SNSZRD, of which eight prototype components (e.g., pachymic acid and senkyunolide G) could cross the BBB. Molecular docking revealed that these components formed stable hydrogen bonds with the SIRT1 protein. SNSZRD treatment significantly ameliorated PCPA-induced anxiety-like behaviors and sleep latency/sleep duration, as well as reduced neuronal degeneration and Nissl body loss in the hypothalamus of treated rats. Additionally, SNSZRD elevated serum melatonin and hypothalamus ATP levels and upregulated the mRNA and protein expression levels of arylalkylamine N-acetyltransferase, SIRT1, PPARγ coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A in the MT-SIRT1-mitochondrial biogenesis pathway.
CONCLUSION
SNSZRD might exert its therapeutic effects on insomnia by modulating MT-SIRT1 axis-regulated mitochondrial biogenesis in rats and might serve as an effective therapeutic agent for insomnia.
Core Tip: This study pioneers the scientific validation of Sini-Suanzaoren decoction (SNSZRD) for insomnia by bridging traditional Chinese medicine (TCM) theory with mitochondrial pathophysiology. We identify 8 blood-brain barrier-penetrating components (e.g., senkyunolide G) that activate the MT-SIRT1 pathway, reversing neuronal mitochondrial dysfunction via dose-dependent upregulation of PPARγ coactivator-1α/nuclear respiratory factor-1/mitochondrial transcription factor A. Crucially, we decode TCM principles: "Soothing liver depression" corresponds to SIRT1 stabilization, while "nourishing heart-spirit" aligns with ATP-dependent synaptic repair. This work establishes SNSZRD as a multi-target mitochondrial regulator, offering novel biomarkers (hypothalamic ATP) and lead compounds for insomnia therapeutics.
