Deciphering Key Pharmacological Pathways of Qingdai Acting on Chronic Myeloid Leukemia Using a Network Pharmacology-Based Strategy

Abstract

Qingdai, a traditional Chinese medicine (TCM) used for the treatment of chronic myeloid leukemia (CML) with good efficacy, has been used in China for decades. However, due to the complexity of traditional Chinese medicinal compounds, the pharmacological mechanism of Qingdai needs further research. In this study, we investigated the pharmacological mechanisms of Qingdai in the treatment of CML using network pharmacology approaches.First, components in Qingdai that were selected by pharmacokinetic profiles and biological activity predicted putative targets based on a combination of 2D and 3D similarity measures with known ligands. Then, an interaction network of Qingdai putative targets and known therapeutic targets for the treatment of chronic myeloid leukemia was constructed. By calculating the 4 topological features (degree, betweenness, closeness, and coreness) of each node in the network, we identified the candidate Qingdai targets according to their network topological importance. The composite compounds of Qingdai and the corresponding candidate major targets were further validated by a molecular docking simulation.Seven components in Qingdai were selected and 32 candidate Qingdai targets were identified; these were more frequently involved in cytokine-cytokine receptor interaction, cell cycle, p53 signaling pathway, MAPK signaling pathway, and immune system-related pathways, which all play important roles in the progression of CML. Finally, the molecular docking simulation showed that 23 pairs of chemical components and candidate Qingdai targets had effective binding.This network-based pharmacology study suggests that Qingdai acts through the regulation of candidate targets to interfere with CML and thus regulates the occurrence and development of CML.

Deciphering the Key Pharmacological Pathways and Targets of Yisui Qinghuang Powder That Acts on Myelodysplastic Syndromes Using a Network Pharmacology‐Based Strategy

“…Network pharmacology is a novel field that integrates pharmacology, biochemistry, genomics, and bioinformatics [ 7 ]. It is an effective strategy to visualize and analyze complex interactive data on herbs, compounds, targets, and diseases based on computer modeling analysis and target prediction methods [ 11 ] and is especially suitable for characterizing TCM formulations. Furthermore, molecular docking is a powerful method used to predict the binding force between the drug compounds and their putative targets based on the spatial structure of the drug and ligand.…”

“…The major bioactive compounds of indigo naturalis are indirubin, indigo, and tryptanthrin. Indirubin exerts anti-inflammatory and antiapoptotic effects and used for the treatment of hematopathies [ 11 ]. The primary ginsenosides in red ginseng are G-Rg1 and G-Rb1, which show weak antitumor activity.…”

“…Network pharmacology integrates systems biology with polypharmacology and is a suitable approach to characterize complex TCM formulations and identify their multiple targets and mechanisms of action [ 7 , 11 ]. We identified the bioactive compounds of YSQHP using the TCMSP [ 12 ] and HerDing databases [ 13 ] and established the network of these compounds, their putative targets, and diseases.…”

Decoding the Mechanism of Huanglian Jiedu Decoction in Treating Pneumonia Based on Network Pharmacology and Molecular Docking

“…The crystal structures of the hub targets were downloaded from the RCSB PDB database 16 , and the structures of the active ingredients were obtained from the TCMSP database. Before molecular docking, the AutoDock 4.2.6 software was used to remove ligands, structure water molecules, and add polar hydrogen atoms and charges to the protein crystal structures ( Li H. Y. et al, 2018 ). The Discovery Studio software was used to evaluate the interaction between the targets and the active ingredients.…”

Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy

“…Yu Ning, et al, through the combination BZYQD with cisplatin in cisplatin-resistant A549/DDP cells, showed that BZYQD exhibited direct cytotoxic and chemosensitising effects, suggesting that cotreatment with BZYQD and cisplatin might reverse cisplatin resistance by inducing ROS accumulation, activating apoptosis and autophagy by oxidative stress [ 10 ]. It was reported that Qingdai acted on a variety of pathways for the treatment of chronic myeloid leukaemia, including cytokine-cytokine receptor interaction, cell cycle, p53 signalling pathway, MAPK signalling pathway, and immune system-related pathways [ 11 ]. Indirubin is the most important and valuable compound in Qingdai; it has been determined to be the quality marker of Qingdai in the Chinese Pharmacopoeia (the State Pharmacopoeia Commission of China, 2015).…”