A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex

Zhenzhen Xue; Yudong Shang; Lan Yang; Tao Li; Bin Yang

doi:10.1016/j.jpha.2024.101066

Volume 15 Issue 4

May 2025

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Zhenzhen Xue, Yudong Shang, Lan Yang, Tao Li, Bin Yang. A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101066. doi: 10.1016/j.jpha.2024.101066

Citation:

Zhenzhen Xue, Yudong Shang, Lan Yang, Tao Li, Bin Yang. A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101066. doi: 10.1016/j.jpha.2024.101066

Citation:

Zhenzhen Xue, Yudong Shang, Lan Yang, Tao Li, Bin Yang. A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101066. doi: 10.1016/j.jpha.2024.101066

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A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex

doi: 10.1016/j.jpha.2024.101066

a. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China;
b. Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 100700, China;
c. Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun, 130022, China;
d. Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, 10070, China

Funds:

The work was supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences, China (Grant Nos.: CI2023E002 and CI2021A04513), the National Natural Science Foundation of China (Grant Nos.: 82204619 and 82274094), and the Fundamental Research Funds for the Central Public Welfare Research Institutes, China (Grant Nos.: ZZ15-YQ-067 and ZZ16-ND-10-26).

Received Date: Apr. 17, 2024
Accepted Date: Aug. 03, 2024
Rev Recd Date: Jul. 22, 2024
Publish Date: Aug. 08, 2024

Abstract

Abstract

A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex (MOC) was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine (TCM). The strategy possessed four characteristics: 1) The tailored database consisted of metabolites derived from big data-originated reference compound, metabolites predicted in silico, and MOC chemical profile-based pseudomolecular ions. 2) When profiling MOC-derived metabolites in vivo, attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds, as reported by most papers, but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites. 3) Metabolite traceability was performed, especially to distinguish isomeric prototypes-derived metabolites, prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds. 4) Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification. Using this strategy, 134 metabolites were swiftly characterized after the oral administration of MOC to rats, and several metabolites were reported for the first time. Furthermore, 17 potential active metabolites were discovered by targeting the motilin, dopamine D2, and the serotonin type 4 (5-HT₄) receptors, and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model. This study extends the application of mass spectrometry (MS) to rapidly profile TCM-derived metabolites in vivo, which will help pharmacologists rapidly discover potent metabolites from a complex matrix.
- Tailored database,
- Metabolite traceability,
- Activity screening,
- Magnoliae Officinalis Cortex,
- In vivo metabolite

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References(39)

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