Network pharmacology of apigeniflavan: a novel bioactive compound of Trema orientalis Linn. in the treatment of pancreatic cancer through bioinformatics approaches

Richa Das; Shreni Agrawal; Pradeep Kumar; Amit Kumar Singh; Praveen Kumar Shukla; Indrani Bhattacharya; Kavindra Nath Tiwari; Sunil Kumar Mishra; Amit Kumar Tripathi

doi:10.1007/s13205-023-03570-7

Network pharmacology of apigeniflavan: a novel bioactive compound of Trema orientalis Linn. in the treatment of pancreatic cancer through bioinformatics approaches

3 Biotech. 2023 May;13(5):160. doi: 10.1007/s13205-023-03570-7. Epub 2023 May 3.

Authors

Richa Das¹, Shreni Agrawal¹, Pradeep Kumar², Amit Kumar Singh³, Praveen Kumar Shukla², Indrani Bhattacharya¹, Kavindra Nath Tiwari², Sunil Kumar Mishra³, Amit Kumar Tripathi⁴

Affiliations

¹ Department of Biotechnology, Parul Institute of Applied Science, Parul University, Vadodara, 391760 Gujarat India.
² Department of Botany, MMV, Banaras Hindu University, Varanasi, 221005 UP India.
³ Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005 UP India.
⁴ School of Basic and Applied Science, Galgotias University, Gautam Buddha Nagar, Noida, 203201 UP India.

Abstract

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.

Keywords: High-resolution mass spectrometry; Hub gene; Molecular docking; Network pharmacology; Pancreatic cancer; Trema orientalis.

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