Network pharmacology and molecular docking to elucidate the mechanism of pulsatilla decoction in the treatment of colon cancer

Abstract

Objective: Colon cancer is a malignant neoplastic disease that seriously endangers the health of patients. Pulsatilla decoction (PD) has some therapeutic effects on colon cancer. This study is based on the analytical methods of network pharmacology and molecular docking to study the mechanism of PD in the treatment of colon cancer.Methods: Based on the Traditional Chinese Medicine Systems Pharmacology Database, the main targets and active ingredients in PD were filtered, and then, the colon cancer-related targets were screened using Genecards, OMIM, PharmGKB, and Drugbank databases. Then, the screened drug and disease targets were Venn analyzed to obtain the intersection targets. Cytoscape software was used to construct the “Components–Targets–Pathway” map, and the String database was used to analyze the protein interaction network of the intersecting targets and screen the core targets, and then, the core targets were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was implemented using AutoDockTools to predict the binding capacity for the core targets and the active components in PD.Results: Sixty-five ingredients containing 188 nonrepetitive targets were screened and 180 potential targets of PD anticolon cancer were identified, including 10 core targets, namely, MAPK1, JUN, AKT1, TP53, TNF, RELA, MAPK14, CXCL8, ESR1, and FOS. The results of GO analysis showed that PD anticolon cancer may be related to cell proliferation, apoptosis, energy metabolism, immune regulation, signal transduction, and other biological processes. The results of KEGG analysis indicated that the PI3K-Akt signaling pathway, MAPK signaling pathway, proteoglycans in cancer, IL-17 signaling pathway, cellular senescence, and TNF signaling pathway were mainly involved in the regulation of tumor cells. We further selected core targets with high degree values as receptor proteins for molecular docking with the main active ingredients of the drug, including MAPK1, JUN, and AKT1. The docking results showed good affinity, especially quercetin.Conclusion: This study preliminarily verified that PD may exert its effect on the treatment of colon cancer through multi-ingredients, multitargets, and multipathways. This will deepen our understanding of the potential mechanisms of PD anticolon cancer and establish a foundation for further basic experimental research.

Pulsatilla Decoction and its bioactive component β-peltatin induce G2/M cell cycle arrest and apoptosis in pancreatic cancer

“…Therefore, to expand the use of TCM formulae into mainstream neccesitates the identification of leading bioactive constituent. Several pieces of preclinical evidence have revealed that PD exhibits anticancer potential [ 4 , 5 ]. However, the principal bioactive constituent responsible for its anti-cancer action is indistinct, due to its intricate multi-constituent nature.…”

“…Modern pharmacological research has demonstrated that PD alleviates various diseases, including diarrhea, inflammatory bowel disease, Escherichia coli infection, vulvovaginal candidiasis, and cancer [ 4 – 10 ]. The preclinical evidence on the anticancer properties of PD mainly focuses on colorectal and colon cancer, while research on other types of cancer remains limited [ 4 , 5 ].…”

Cortex Mori extracts induce apoptosis and inhibit tumor invasion via blockage of the PI3K/AKT signaling in melanoma cells

“…Anti-tumor properties of Sanggenon C have also been described in leukemia by inducing cell cycle arrest and cell death ( Huang et al, 2011 ). Quercetin has anti-tumor activity in a variety of cancers, including non-small cell lung cancer, colorectal cancer, and others ( Li et al, 2022 ; Liu et al, 2022 ). Kaempferol also has anti-tumor properties due to its modulation of the Akt/mTOR signaling and FAK pathways ( Hung et al, 2017 ; Wang et al, 2021 ).…”

Exploring the potential mechanism of Fritiliariae Irrhosae Bulbus on ischemic stroke based on network pharmacology and experimental validation

“…The active chemical components of FIB were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, http://tcmspw.com/index.php ) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP, http://www.tcmip.cn/TCMIP/index.php/Home/Login/login.html ). According to the oral bioavailability (OB) of the drug ≥30% and the drug similarity (DS) ≥0.18, the active ingredients of FIB were further screened out ( Liu et al, 2022 ). According to the two databases, we have integrated the targets involved in the active ingredients, and performed the comparison of target information and target name correction through the UniProt database ( https://www.uniprot.org ), then made a conversion of the targets into a unified gene name, defining the source of the gene to “ Homo sapiens ”.…”

“…The degree of a node is related to the number of edges which connected to the node. The larger the degree centrality (DC), the more nodes in the network related to the node directly, and then the more important the node in the network ( Liu et al, 2022 ).…”