Network pharmacology of apigeniflavan: a novel bioactive compound of Trema orientalis Linn. in the treatment of pancreatic cancer through bioinformatics approaches.
Richa DasShreni AgrawalPradeep KumarAmit Kumar SinghPraveen Kumar ShuklaIndrani BhattacharyaKavindra Nath TiwariSunil Kumar MishraAmit Kumar TripathiPublished in: 3 Biotech (2023)
Pancreatic cancer is the seventh most prevalent cause of mortality globally. Since time immemorial, plant-derived products have been in use as therapeutic agents due to the existence of biologically active molecules called secondary metabolites. Flavonoids obtained from plants participate in cell cycle arrest, induce autophagy and apoptosis, and decrease oxidative stress in pancreatic cancer. The present study involves network pharmacology-based study of the methanolic leaf extract of Trema orientalis ( MLETO) Linn. From the high-resolution mass spectrometry (HRMS) analysis, 21 nucleated flavonoids were screened out, of which only apigeniflavan was selected for further studies because it followed Lipinski's rule and showed no toxicity. The pharmacokinetics and physiochemical characteristics of apigeniflavan were performed using the online web servers pkCSM, Swiss ADME, and ProTox-II. This is the first in silico study to report the efficiency of apigeniflavan in pancreatic cancer treatment. The targets of apigeniflavan were fetched from SwissTargetPrediction database. The targets of pancreatic cancer were retrieved from DisGeNET and GeneCards. The protein-protein interaction of the common genes using Cytoscape yielded the top five hub genes: KDR, VEGFA, AKT1, SRC, and ESR1. Upon molecular docking, the lowest binding energies corresponded to best docking score which indicated the highest protein-ligand affinity. Kyoto Encyclopaedia of Genes and Genomes (KEGG) database was employed to see the involvement of hub genes in pathways related to pancreatic cancer. The following, pancreatic cancer pathway, MAPK, VEGF, PI3K-Akt, and ErbB signaling pathways, were found to be significant. Our results indicate the involvement of the hub genes in tumor growth, invasion and proliferation in the above-mentioned pathways, and therefore necessitating their downregulation. Moreover, apigeniflavan can flourish as a promising drug for the treatment of pancreatic cancer in future.
Keyphrases
- signaling pathway
- pi k akt
- cell cycle arrest
- molecular docking
- oxidative stress
- bioinformatics analysis
- protein protein
- cell death
- genome wide
- cell proliferation
- high resolution mass spectrometry
- induced apoptosis
- small molecule
- genome wide identification
- endoplasmic reticulum stress
- molecular dynamics simulations
- emergency department
- dna methylation
- cardiovascular events
- adverse drug
- tyrosine kinase
- molecular dynamics
- electronic health record
- density functional theory
- heat shock protein
- mass spectrometry
- diabetic rats