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Updated: Nov 11, 2025

Author Spotlight: Developing a Simple and Robust Hepatic Model for Pharmacological and Toxicological Applications
Published on: October 20, 2023
A metabolic data-driven systems pharmacology strategy for decoding and validating the mechanism of Compound Kushen
Ke-Xin Wang1, Yu-Peng Chen2, Ai-Ping Lu3
1Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.
Ethnopharmacological Relevance:
Compound Kushen Injection (CKI) is a widely used TCM formula for treatment of carcinomatous pain and tumors of digestive system including hepatocellular carcinoma (HCC). However, the potential mechanisms of CKI for treatment of HCC have not been systematically and deeply studied.
Aim Of Study:
A metabolic data-driven systems pharmacology approach was utilized to investigate the potential mechanisms of CKI for treatment of HCC.
Materials And Methods:
Based on phenotypic data generated by metabolomics and genotypic data of drug targets, a propagation model based on Dijkstra program was proposed to decode the effective network of key genotype-phenotype of CKI in treating HCC. The pivotal pathway was predicted by target propagation mode of our proposed model, and was validated in SMMC-7721 cells and diethylnitrosamine-induced rats.
Results:
Metabolomics results indicated that 12 differential metabolites, and 5 metabolic pathways might be involved in the anti-HCC effect of CKI. A total of 86 metabolic related genes that affected by CKI were obtained. The results calculated by propagation model showed that 6475 shortest distance chains might be involved in the anti-HCC effect of CKI. According to the results of propagation mode, EGFR was identified as the core target of CKI for the anti-HCC effect. Finally, EGFR and its related pathway EGFR-STAT3 signaling pathway were validated in vivo and in vitro.
Conclusion:
The proposed method provides a methodological reference for explaining the underlying mechanism of TCM in treating HCC.
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