Insights into the antineoplastic mechanism of Chelidonium majus via systems pharmacology approach

Abstract

Background: The antineoplastic activity of Chelidonium majus has been reported, but its mechanism of action (MoA) is unsuspected. The emerging theory of systems pharmacology may be a useful approach to analyze the complicated MoA of this multi-ingredient traditional Chinese medicine (TCM).

Methods: We collected the ingredients and related compound-target interactions of C. majus from several databases. The bSDTNBI (balanced substructure-drug-target network-based inference) method was applied to predict each ingredient’s targets. Pathway enrichment analysis was subsequently conducted to illustrate the potential MoA, and prognostic genes were identified to predict the certain types of cancers that C. majus might be beneficial in treatment. Bioassays and literature survey were used to validate the in silico results.

Results: Systems pharmacology analysis demonstrated that C. majus exerted experimental or putative interactions with 18 cancer-associated pathways, and might specifically act on 13 types of cancers. Chelidonine, sanguinarine, chelerythrine, berberine, and coptisine, which are the predominant components of C. majus, may suppress the cancer genes by regulating cell cycle, inducing cell apoptosis and inhibiting proliferation.

Conclusions: The antineoplastic MoA of C. majus was investigated by systems pharmacology approach. C. majus exhibited promising pharmacological effect against cancer, and may consequently be useful material in further drug development. The alkaloids are the key components in C. majus that exhibit anticancer activity.

Graphical abstract

Keywords

systems pharmacology / mechanism of action / traditional Chinese medicine / Chelidonium majus

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ACKNOWLEDGEMENTS

This work was supported by the National Key Research and Development Program of China (No. 2016YFA0502304), the National Natural Science Foundation of China (Nos. 81673356 and U1603122) and the 111 Project (No. B07023).

COMPLIANCE WITH ETHICS GUIDELINES

The authors Xinzhe Xiao, Zehui Chen, Zengrui Wu, Tianduanyi Wang, Weihua Li, Guixia Liu, Bo Zhang and Yun Tang declare that they have no conflict of interests.ƒThis article does not contain any studies with human or animal subjects performed by any of the authors.

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