Research Paper Volume 14, Issue 22 pp 9103—9127

Exploring the mechanisms underlying the therapeutic effect of the Radix Bupleuri-Rhizoma Cyperi herb pair on hepatocellular carcinoma using multilevel data integration and molecular docking

Luzhi Qing1, *, , Botao Pan1, *, , Yanjun He1,2, , Yu Liu1, , Minhong Zhao1, , Bo Niu1, &, , Xiuan Gao1, ,

  • 1 Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan 528000, PR China
  • 2 Emergency Department, Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan 528000, PR China
* Equal contribution

Received: July 26, 2022       Accepted: November 7, 2022       Published: November 18, 2022
How to Cite

Copyright: © 2022 Qing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Traditional Chinese medicine (TCM) is a promising and effective treatment for cancer with minimal side effects through a multi-active ingredient multitarget network. Radix Bupleuri and Rhizoma Cyperi are listed as herbs dispersing stagnated liver Qi in China. They have been used clinically to treat liver diseases for many years and recent pharmacological studies have shown that they inhibit the proliferation of hepatocellular carcinoma (HCC). However, the pharmacological mechanisms, potential targets, and clinical value of the Radix Bupleuri-Rhizoma Cyperi herb pair (CXP) for suppressing HCC growth have not been fully elucidated. We identified 44 CXP targets involved in the treatment of HCC using the GEO dataset and HERB database. An analysis of the Traditional Chinese Medicine System Pharmacology Database (TCMSP) showed that CXP exerts synergistic effects through 4 active ingredients, including quercetin, stigmasterol, isorhamnetin, and kaempferol. GO and KEGG analyses revealed that CXP mainly regulates HCC progression through metabolic pathways, the p53 signaling pathway, and the cell cycle. Additionally, we applied The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) database to perform the expression patterns, clinical features, and prognosis of 6 genes (CCNB1, CDK1, CDK4, MYC, CDKN2A, and CHEK1) in cell cycle pathways to reveal that CXP suppresses HCC clinical therapeutic value. Moreover, based on molecular docking, we further verified that CXP exerts its anti-HCC activity through the interaction of multiple active components with cell cycle-related genes. We systematically revealed the potential pharmacological mechanisms and targets of CXP in HCC using multilevel data integration and molecular docking strategies.


HBV: Hepatitis B virus; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; TCM: Traditional Chinese Medicine; CXP: Radix Bupleuri (Chaihu)-Rhizoma Cyperi (Xiangfu) herb pair; CSS: Chaihu Shugan San; NAFLD: Non-alcoholic fatty liver disease; TCMSP: Traditional Chinese Medicine System Pharmacology; OB: Oral bioavailability; DL: Drug-likeness; ADME: Absorption, distribution, metabolism, and excretion; DEGs: differentially expressed genes; FDR: False discovery rate; LIHC: Liver hepatocellular carcinoma; TCGA: The Cancer Genome Atlas; FPKM: Fragments per kilobase per million; TPM: Transcripts per million; OS: Overall survival; DSS: Disease-specific survival; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: Protein-protein interaction; MCODE: Molecular Complex Detection; H-C-T: Herb-Compounds-Targets; K-G: KEGG pathway-Genes; PDB: Protein Data Bank; UAMP: Uniform Manifold Approximation and Projection; ROC: receiver operating characteristic; AUC: areas under the curve; LASSO: Least absolute shrinkage and selection operator.