Unveiling the ‘Eating Poison’ of <i>Polygala tenuifolia</i> xylem: Mood changes and myocardial injury

Fusheng Zhang; Lijun Zhang; Wei Mao; Yunzhi Ma; Yingxin Lou; Xiaoying Li; Huan Liu; Lin Zhao; Dingding Guo; Zhenyu Li

doi:10.1016/j.jpha.2025.101466

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Fusheng Zhang, Lijun Zhang, Wei Mao, Yunzhi Ma, Yingxin Lou, Xiaoying Li, Huan Liu, Lin Zhao, Dingding Guo, Zhenyu Li. Unveiling the ‘Eating Poison’ of Polygala tenuifolia xylem: Mood changes and myocardial injury[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101466

Citation:

Fusheng Zhang, Lijun Zhang, Wei Mao, Yunzhi Ma, Yingxin Lou, Xiaoying Li, Huan Liu, Lin Zhao, Dingding Guo, Zhenyu Li. Unveiling the ‘Eating Poison’ of Polygala tenuifolia xylem: Mood changes and myocardial injury[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101466

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Unveiling the ‘Eating Poison’ of Polygala tenuifolia xylem: Mood changes and myocardial injury

doi: 10.1016/j.jpha.2025.101466

a. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, China;
b. Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, 030006, China;
c. Drug Safety Evaluation Center in China Institute for Radiation Protection, Taiyuan Shanxi, 030006, China;
d. Shanxi Provincial Institute of TCM, Taiyuan, 030045, China

Funds:

This work was supported by the Fundamental Research Program of Shanxi Province, China (Grant No.: 202403021211184), the Shanxi Province Scientific and Technological Achievements Transformation Special Project (Project No.: 202104021301064), the 2024 Traditional Chinese Medicine Research Program (Grant No.: 2024ZYY2A030), the 2025 Shanxi Province Traditional Chinese Medicine Industry Modernization Support Project (Project No.: 2025zyycy04), the Traditional Chinese Medicine Innovation Team of Shanxi Province, China (Grant No.: zyytd2024020).

Received Date: Mar. 18, 2025
Accepted Date: Oct. 07, 2025
Rev Recd Date: Oct. 06, 2025
Available Online: Oct. 10, 2025

Abstract

Abstract

The precise processing methods of traditional Chinese herbal medicines are paramount to ensuring their safety and efficacy. Leigong PaoZhi Lun, the seminal work on the processing of Chinese herbal medicine, documents that the ingestion of Polygala tenuifolia Xylem (PTX) induces a state referred to as "MEN". However, the biological phenotypic effects of PTX-induced "MEN" and its underlying mechanisms remain largely unexplored. This study employs a comprehensive approach, integrating behavioral observations related to the central nervous system (CNS) and cardiovascular system (CVS), electrocardiogram analysis, myocardial enzyme detection, Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS)-based metabolomics, plasma exosomal microRNA (miRNA) sequencing, intracerebral cannulation of the lateral habenula (LHb) with administration of the N-Methyl-D-Aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonopentanoic acid (AP5), molecular docking, and a combination of in silico and wet lab experiments. This multifaceted methodology unveiled the chemical phenotype of PTX, identifying 245 chemical constituents, including 7 specific metabolites. Two key findings emerged: PTX disrupts the glutamate (Glu)-gamma-aminobutyric acid (GABA) balance within the LHb, leading to CNS-related depressive-like mood alterations. Additionally, tenuifolin and sibiricose A5 in PTX mediate aldehyde dehydrogenase 2 (ALDH2) inactivation, resulting in CVS-related myocardial cell damage, subsequently causing increased heart rate and hypoxia. These findings provide a novel research perspective on the "safety" quality control and evaluation of P. tenuifolia. Additionally, they offer new evidence to elucidate the modern scientific implications of the theories of "same origin with different effects" and "co-existence of opposite properties" in traditional Chinese medicine.
- Polygala tenuifolia Xylem,
- Eating poison,
- Depressive-anxiety-like mood changes,
- Increased heart rate,
- Hypoxia

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References(49)

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