Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Compound Kushen Injection in Anti-Cancer Effect

Abstract

Departmental sources Background:Compound Kushen injection (CKI) is a traditional Chinese medicine preparation for clinical treatment of cancer pain or treatment of various types of solid tumors. The purpose of this study was to identify the main active compounds from CKI and to investigate its anti-cancer mechanisms via drug target biological network pharmacology construction and prediction. Material/Methods:Constituents of CKI were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets were collected in the Human Gene (Gene Cards) and Human Mendelian Inheritance (OMIM) databases. "Ingredients-protein targets-pathway" networks were constructed using Cytoscape. STRING database platform to construct enrichment of protein-protein interactions (PPI), related diseases and pathways network. Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of were performed to investigate by using Bioconductor tool for analysis. Results:The results indicated that 60 constituents of absorption, distribution, metabolism, and excretion (ADME) filtration resulted in 33 constituents exhibiting significant correlations with anti-cancer and CKI may target 113 proteins, including IL6, EGFR, CASP3, VEGFA, MYC, and ESR1. GO and KEGG enrichment analysis results show that 129 biological processes and 93 signal pathways associated with cancer. It mainly involves cancers such as prostate cancer, bladder cancer, hepatocellular carcinoma, colorectal cancer, breast cancer, etc. Active ingredients might also induce apoptosis in cancer cells via the p53 and PI3K-Akt signaling pathway mechanism. Conclusions:This study was based on pharmacological networks results for the prediction of the multi-constituent, multitarget, and multi-pathway mechanisms of CKI, which might be a promising potential therapeutic and prevention candidate for anti-cancer. However, based on computer data mining and analysis, this study still needs to be further verified by in vivo/in vitro experiments, and the safety of CKI needs to be evaluated.

An Investigation of the Molecular Mechanisms Underlying the Analgesic Effect of Jakyak‐Gamcho Decoction: A Network Pharmacology Study

“…Because of the complex pharmacological nature of multicompound-multitarget-multipathway agents, there is often a fundamental limitation in investigating their comprehensive mechanisms of action based only on conventional biological experimental methodologies [61][62][63][64][65][66][67][68]. To overcome such challenges, network pharmacology, an integrative research field that systematically combines computational systems biology, network science, medicine, pharmacology, mathematics, and physics, has emerged as one of the most effective approaches for the mechanistic exploration of polypharmacological drugs, such as herbal medicines [61][62][63][64][65][66][67][68]. e goal of this integrative science is to unveil the mechanisms of disease pathogenesis and drug activity that are coordinated through the interactions among diverse biological components such as genes, proteins, cells, tissues, and organs [61][62][63][64][65][66][67][68].…”

“…To overcome such challenges, network pharmacology, an integrative research field that systematically combines computational systems biology, network science, medicine, pharmacology, mathematics, and physics, has emerged as one of the most effective approaches for the mechanistic exploration of polypharmacological drugs, such as herbal medicines [61][62][63][64][65][66][67][68]. e goal of this integrative science is to unveil the mechanisms of disease pathogenesis and drug activity that are coordinated through the interactions among diverse biological components such as genes, proteins, cells, tissues, and organs [61][62][63][64][65][66][67][68]. Previous network pharmacology studies successfully investigated the polypharmacological properties of herbal drugs by identifying their active compounds and key therapeutic targets and further elucidating the distinct system-level pharmacological effects and mechanisms (e.g., therapeutic modulation of biological processes such as proliferation, apoptosis, cell cycle regulation, angiogenesis, oxidation and reduction, insulin metabolism, and inflammation) for the treatment of various diseases, including cancer, diabetes, arthritis, and ischemic stroke, which are exerted by the synergistic interplay between multiple compounds and targets contained in herbal drugs [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79].…”

The Yunnan national medicine Maytenus compound inhibits the proliferation of hepatocellular carcinoma (HCC) by suppressing the activation of the EGFR-PI3K-AKT signaling pathway

“…We found that the Maytenus compound may inhibit HCC cell proliferation by downregulating the EGFR-PI3K-AKT signaling pathway, but its specific direct targets are unknown, requiring further studies. Studies have shown that many traditional Chinese medicines generate anticancer activities through multiple targets 33 , 34 . Therefore, there are other possible molecular mechanisms by which Maytenus compound inhibits HCC proliferation.…”

Cell Cycle Arrest, An Important Mechanism of Action of Compound Kushen Injection, Prevents Colorectal Cancer: Network Pharmacology Analysis and Experimental Validation

“…A TCM network pharmacology approach provides a new research paradigm for translating TCM from experience-based medicine to evidence-based medicine, which will likely accelerate TCM discovery and improve drug discovery strategies 15 . A combination of network pharmacology and experimental verification has gradually become an important way to study the mechanism of action of CKI [16][17][18] .…”