Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma

Abstract

Background This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC 50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC 50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusion As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effects through multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

Network Pharmacology Prediction and Pharmacological Verification Mechanism of Yeju Jiangya Decoction on Hypertension

“…en, the CIF target and hypertension target are mapped, and the Venny map (Venny 2.1) is drawn to get the intersection target of CIF and hypertension, which can be used as the potential target of CIF in the treatment of hypertension. e chemical components and intersection targets of CIF were imported into Cytoscape 3.7.1 software to construct the active component target network, and the topological properties of the network were analyzed; the intersection targets were uploaded to STRING v11.0 database, the species was limited to "human," the confidence was 0.4, the free nodes were deleted, and the protein-protein interaction (PPI) network was constructed [28][29][30][31][32].…”

“…The chemical components and intersection targets of CIF were imported into Cytoscape 3.7.1 software to construct the active component target network, and the topological properties of the network were analyzed; the intersection targets were uploaded to STRING v11.0 database, the species was limited to “human,” the confidence was 0.4, the free nodes were deleted, and the protein-protein interaction (PPI) network was constructed [ 28 – 32 ].…”

Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

“…The Search Tool for the Retrieval of Interacting Genes (STRING) database ( https://string-db.org/ ) can explore and analyze direct and indirect interactions between proteins [ 16 ]. Based on the overlapping targets of GZD and hypertension, we constructed the protein–protein interaction (PPI) network by using the STRING 11.0 database with the species limited to “Homo sapiens” and confidence score > 0.4 [ 19 ].…”

“…Therefore, the application of network pharmacology can provide a scientific basis for the in-depth study of TCM prescriptions [ 14 ]. Increasing evidence supports the reliability of the network pharmacology method, which may be an effective way to study the pharmacological mechanisms of TCM prescriptions [ 16 , 17 ].…”