Network pharmacology and Molecular docking-based activity of Hemidesmus indicus (L.) R.Br. in Acute myeloid leukemia : A Computational Study

Abstract

ABSTRACT Background Acute myeloid leukemia (AML) is malignancy of the stem cell precursors of the myeloid lineage occurs due to variations in genetics. Incidence rate of childhood AML in Asian population is 8.4 per million. There is no exact description of AML is Ayurveda, it can be considered into Raktapitta (~bleeding disorder) disease. Hemidesmus indicus (L.) R.Br. (~H. indicus) is described for treatment of Raktapitta. The main treatment for AML is chemotherapy, and patient are searching for Ayurvedic medicines. Hence attempt is made for evaluating activity of H. indicus in AML. Objective To establish link for therapeutic activity of H. indicus in AML using Network pharmacology and molecular docking study. Materials and methods Active compound from root of H. indicus was retrieved from phytochemical based IMPPAT database. ADME (absorption, distribution, metabolism and excretion) study of retrieved active compound done with SwissADME database, and ADME qualified active compound target were obtained with having probability >0.7 from SwissTargetPrediction database. Target of AML retrieved from GeneCard database having relevancy score ≥5.0. To take the common, target of active compound and AML targets from GeneCard are imported into the Venny2.1 database, and the resulting targets used for the analysis. Cytoscape3.9.1 software was used to construct the "drug-active components-target" network diagram from common targets. The PPI (protein-protein interaction) network between proteins was constructed by STRING and result exported to Cytoscape3.9.1 for network analysis to get subnetwork with key target of subnetwork and core targets of overall PPI. GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis of key target from subnetwork done with g-profiler database. Core targets were docked with their corresponding active compound to get docking score. Results Total of 66 active compound were obtained from H. indicus, On ADME screening 49 active compounds qualified. ADME qualified active compound screened for target and 149 target obtained, after removal of duplicates 81 target were remained. 806 targets of AML were screened from GeneCard database. 19 common targets were obtained between target of active compound and target of AML from GeneCard. These screened 19 targets imported in STRING database to construct PPI network, and obtained result imported into Cytoscape3.9.1 for network analysis, on analysis 1 sub networks with 11 key targets were obtained. Top five H. indicus core targets for AML obtained using “CytoHubba” plug-in. GO and KEGG enrichment analyses were performed on the above-mentioned 11 key targets from sub network, 44 MF (Molecular function), 166 BP (Biological process), 12 CC (Cellular component) and 55 pathways were obtained from the KEGG pathway analyses. Molecular docking results showed that the active component quercetin could spontaneously bind to the core targets EGFR, SRC, AKT1, KDR and IGF1R. EGFR has the best combination with quercetin. Conclusion All core targets identified through network analysis of PPI network were linked to common active compound quercetin, and on molecular docking study all core targets showed good docking score to quercetin. Hence, based on this study conclusion can be drawn that the activity of H. indicus is AML might be due to presence of quercetin active compound in it. This study generated link for usefulness of H. indicus is AML.