Combination of Metabolite Analysis and Network Pharmacology to Explore the Potential Anticough Mechanism of Protopine—A Marker in Zhi-Ke-Bao Tablets

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS Rapid Communications in Mass Spectrometry Pub Date : 2025-02-18 DOI:10.1002/rcm.10012

Qi-Feng Zou, De-Jian Chen, Cheng-Jun Liu, Zi-Hao Chen, Xia Yang, Rong-Huang Xu, Zhen-Hui Zhou, Jian-Xin Chen, Wei Shi, Feng-Xiang Zhang

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引用次数: 0

Abstract

Rationale

Protopine, an active alkaloid in Papaver somniferum L., was abundant in a well-known anticough traditional Chinese medicine preparation—Zhi-Ke-Bao tablets. Till now, the metabolism feature and anticough mechanism of protopine have not been fully elucidated, restricting its further development.

Methods

The metabolites of protopine in rats were profiled by using ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry, and its anticough targets and mechanism were predicted by network pharmacology.

Results

In rats, a total of 19 metabolites were identified following ingestion of protopine (21 mg/kg/day, i.g.), including 4 in plasma, 6 in urine, 5 in feces, 10 in liver, 2 in spleen, 4 in lung, 3 in kidney, 3 in heart, and 3 in brain. The main metabolic features were ring-opening, methylation, demethylation, glucuronidation, sulfation, and hydroxylation. Among them, methylation, sulfation, and hydroxylation of protopine in vivo were revealed for the first time. The network pharmacology results show that protopine and its metabolites regulate physiological activities by acting on STAT3, SRC, CASP3, MTOR, MMP9, ESR1, and other targets, involving PI3K-Akt signaling pathway, FoxO signaling pathway, and TNF signaling pathway, etc.

Conclusions

The metabolic features of protopine and its potential mechanisms for anticough effects were outlined, providing data for further anticough pharmacological validation of protopine.

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来源期刊

Rapid Communications in Mass Spectrometry 化学-分析化学

CiteScore

4.10

自引率

5.00%

发文量

219

审稿时长

2.6 months

期刊介绍： Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.