Network Pharmacology-Based Prediction and Verification of the Active Ingredients and Potential Targets of Zuojinwan for Treating Colorectal Cancer.

Background: Zuojinwan (ZJW), a famous Chinese medicine formula, has been widely used to treat colorectal cancer (CRC). However, its bioactive compounds, potential targets, and molecular mechanism remain largely elusive.

Aim: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation were employed to investigate bioactive compounds, potential targets, and molecular mechanism of ZJW against CRC.

Materials And Methods: Bioactive compounds and potential targets of ZJW, as well as related genes of CRC, were acquired from public databases. Important ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the findings.

Results: A total of 36 bioactive ingredients of ZJW and 163 gene targets of ZJW were identified. The network analysis revealed that quercetin, baicalein, wogonin, beta-sitosterol, and isorhamnetin may be candidate agents. The AKT1, JUN, CDKN1A, BCL2L1, and NCOA1 could become potential drug targets. The KEGG indicated that PI3K-AKT signaling pathway may play an important role in the effect of ZJW against CRC. Molecular docking suggested that quercetin, baicalein, and wogonin combined well with AKT1 and JUN. The in vitro experiment showed that quercetin, the most important ingredient of ZJW, could induce apoptosis of HCT116 cells through PI3K-Akt signaling pathway. This finding was congruent with the prediction obtained through the network pharmacology approach.

Conclusion: This study comprehensively illuminated the active ingredients, potential targets, and molecular mechanism of ZJW against CRC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of traditional Chinese medicine (TCM) formula treating for disease.