Metabolic difference of potentially toxic components from Psoraleae Fructus and Euodiae Fructus in Sishen formula by different compatibilities and physiologies

Lili Hong; Yijin Yang; Lianxing Wang; Yiqing Yao; Yadan Zou; Hongda Wang; Xue Li; Yuan Li; Lingli Ma; Xiaoying Wang; Xiumei Gao; Wenzhi Yang

doi:10.1016/j.jpha.2025.101467

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Lili Hong, Yijin Yang, Lianxing Wang, Yiqing Yao, Yadan Zou, Hongda Wang, Xue Li, Yuan Li, Lingli Ma, Xiaoying Wang, Xiumei Gao, Wenzhi Yang. Metabolic difference of potentially toxic components from Psoraleae Fructus and Euodiae Fructus in Sishen formula by different compatibilities and physiologies[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101467

Citation:

Lili Hong, Yijin Yang, Lianxing Wang, Yiqing Yao, Yadan Zou, Hongda Wang, Xue Li, Yuan Li, Lingli Ma, Xiaoying Wang, Xiumei Gao, Wenzhi Yang. Metabolic difference of potentially toxic components from Psoraleae Fructus and Euodiae Fructus in Sishen formula by different compatibilities and physiologies[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101467

Citation:

Lili Hong, Yijin Yang, Lianxing Wang, Yiqing Yao, Yadan Zou, Hongda Wang, Xue Li, Yuan Li, Lingli Ma, Xiaoying Wang, Xiumei Gao, Wenzhi Yang. Metabolic difference of potentially toxic components from Psoraleae Fructus and Euodiae Fructus in Sishen formula by different compatibilities and physiologies[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101467

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Metabolic difference of potentially toxic components from Psoraleae Fructus and Euodiae Fructus in Sishen formula by different compatibilities and physiologies

doi: 10.1016/j.jpha.2025.101467

Lili Hong^a,b,
Yijin Yang^a,b,
Lianxing Wang^a,b,
Yiqing Yao^a,b,
Yadan Zou^a,b,
Hongda Wang^a,b,c,
Xue Li^a,b,
Yuan Li^a,b,
Lingli Ma^a,b,
Xiaoying Wang^a,b,c,
Xiumei Gao^{a,b,c
,
,},
Wenzhi Yang^{a,b,c
,
,}

a. State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China;
b. Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China;
c. Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant No.: 82192914), Tianjin Committee of Science and Technology, China (Grant No.: 24ZYJDSS00310), Special Project for Technological Innovation in New Productive Forces of Modern Chinese Medicines (Grant No.: 24ZXZKSY00010), and Tianjin Outstanding Youth Fund (Grant No.: 23JCJQJC00030).

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

Abstract

Abstract

Compatibility attenuation is an effective strategy to ensure the safety of traditional Chinese medicine (TCM). Mechanistic elucidation is essential, however, no consensus reaches on the scientific connotation of compatibility attenuation in Sishen formula (SSF). Given TCM metabolism is closely associated with its toxicological consequences, this study was designed to systematically decipher and compare the holistic metabolic differences of potential toxicants derived from Psoraleae Fructus (PF) and Euodiae Fructus (EF) within SSF. In total, 23 potential toxicants from PF and EF were identified through a comprehensive literature review. Using ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry and ultra-high performance liquid chromatography/triple quadrupole-linear ion trap mass spectrometry, the metabolic difference of target components among differentiated compatibility and physiological state was elucidated by integrating serum metabolomics and poly-pharmacokinetics analyses. Holistically, the compatibility could suppress the transformation of potential toxicants, whereas irritable bowel syndrome (IBS) state exhibited a promoting effect. Myristicae Semen (MyS) or Schisandrae Chinensis Fructus (SCF) increased the exposure of toxicants from PF, while EF demonstrated an opposing effect. SCF promoted the exposure of toxicants from EF, which could be mitigated by Ershen formula. The IBS mice exhibited greater exposure to potential toxicants and their metabolites from PF (compared to the sham operation group), yet SSF alleviated this effect. Furthermore, potential toxicants in the SSF group tended to exhibit reduced metabolic transformation, decreased exposure, enhanced tissue distribution, and facilitated excretion. Collectively, these findings provide novel insights into the metabolic mechanisms underlying SSF detoxification and offer valuable safety recommendation in clinical use.

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References(49)

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