Title:Network Pharmacology Study on the Underlying Mechanism of Danggui–Kushen Herb Pair in Adjuvant Chemotherapeutics against Breast Cancer
Volume: 28
Issue: 2
Author(s): Yijuan Hu, Jiaolong He and Yunling Xu*
Affiliation:
- Key Laboratory of Research and Development of Chinese Medicine of Zhejiang Province, Zhejiang Academy of Traditional
Chinese Medicine, Hangzhou, 310007, China
Keywords:
Network pharmacology, danggui–kushen herb pair, breast cancer, molecular docking, traditional chinese medicine, molecular mechanism.
Abstract:
Background: The Danggui–Kushen herb pair (DKHP) is a classic prescription that has
long been used in combination with chemotherapeutic drugs to improve the immune status of patients
with breast cancer (BC), however, the active components and the underlying pharmacological
mechanisms remain unclear. Therefore, this study aimed to elucidate the possible mechanism
of action of DKHP against BC-based comprehensive strategy combining network pharmacology,
molecular docking, and cellular experiments.
Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform
was used to obtain the relevant compounds in DKHP. Genecards and the National Center for
Biotechnology Information databases were used to predict BC targets. Then, drug–compound–
target, and protein–protein interaction networks were constructed to forecast the promising protein
targets of DKHP and identify the primary interactions that occur between the protein targets and
compounds. Finally, the predicted candidate targets were validated using docking techniques and
in vitro experiments.
Results: A total of 30 potential active compounds and 173 intersecting pharmacological targets
were identified in DKHP. Gene Ontology enrichment analysis revealed that the inflammatory response,
positive regulation of protein phosphorylation, and cellular response to lipopolysaccharide
were closely related to DKHP treatment in BC. Kyoto Encyclopedia of Genes and Genomes pathway
analysis suggested that the PI3K/AKT pathway may be crucial for DKHP intervention in BC.
Therefore, key targets could be AKT1, TP53, VEGR, CASP3, TNF, and IL6. Molecular docking
analysis suggested that hyperforin, kushenin, and kushenol T had good binding ability to Akt, p53,
and Caspase 3. The in vitro experiment showed that the DKHP extract promoted the apoptosis of
MCF-7 cells via the PI3K/Akt signaling pathway. These results corresponded to the predictions
produced using the network pharmacology approach.
Conclusion: Hyperforin, kushenin, kushenol T, and other active compounds in DKHP can regulate
multiple signaling pathways and targets, such as AKT1, TP53, and CASP3, thereby playing preventive
and therapeutic roles in BC.
