Anticancer Effect of Radix Astragali on Cholangiocarcinoma In Vitro and Its Mechanism via Network Pharmacology

Abstract

Background:This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. Material/Methods:We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The componentstargets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. Results:Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA.The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. Conclusions:RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.

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].…”

Therapeutics for Chemotherapy-Induced Peripheral Neuropathy: Approaches with Natural Compounds from Traditional Eastern Medicine

“…Lee et al showed the other Astragalus-based herbal prescription (SH003) could alleviate docetaxel-induced neuropathic pain [ 138 ]. Studies also showed that the components included in Astragali radix have an anti-cancer effect [ 139 , 140 ] and help to prevent nephrotoxicity and hepatotoxicity induced by the anti-cancer drugs [ 73 ]. These further suggest the usefulness of this substance in anti-cancer therapy.…”

A Network Pharmacology Study to Uncover the Mechanism of FDY003 for Ovarian Cancer Treatment

“…This research approach produces distinct types of herbal-drug-associated networks by merging relevant comprehensive pharmacological, medicinal, and biomolecular data 10-17 . This is followed by an investigation of the topological and functional characteristics of the networks, which contributes to the systematic understanding of the treatment mechanisms of herbal drugs 10-17 . Using network pharmacology, we determined the anti-OC potential of FDY003 from a comprehensive systems view.…”