Unraveling the Multi-Target Pharmacological Mechanism of Brassica rapa in Diabetes Treatment: Integration of Network Pharmacology and Molecular Docking Approaches

Abstract

Brassica rapa has been widely reported as an anti-diabetic plant and is widely used in traditional medicine for the treatment of various disorders. However, the molecular mechanism underlying the plant's anti-diabetic activity has not been elucidated. Therefore, the present study aimed to investigate the possible molecular mechanism of B.rapa for managing diabetes mellitus through network pharmacology and molecular docking studies. The active ingredients and associated target proteins were obtained from a literature review and the Swiss Target Prediction platform and validated using the PubChem database. The disease-associated genes were retrieved from the Genecard database. The B. rapa-DM target network was analyzed using the STRING database, and the results were integrated and visualized using Cytoscape software. The molecular mechanism and therapeutic effect of B.rapa for the treatment of DM were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the Enrichr Platform. Fifty-two active ingredients were screened from B. rapa, and 1528 putative target genes were identified from these ingredients. Four hundred and fifty-four overlapping targets matched with DM were considered potential therapeutic targets. First, ten key targets (ALB, AKT1, TNF, GAPDH, MAPK3, EGFR, VEGFA, CTNNB1, CASP3, and STAT3) were found by topological analysis. Then, the results of GO and KEGG suggested that the anti-diabetes effect of B. rapa was strongly associated with the AGE-RAGE signaling pathway in diabetic complications, Neuroactive ligand-receptor interaction, Lipid and atherosclerosis, PI3K-Akt signaling pathway, and Calcium signaling pathway. The AKT1 (Serine/Threonine Protein Kinase) enzyme is targeted by major bioactive constituents of B.rapa. Molecular Docking studies revealed that Liquiritin (docking score -6.1 Kcal/mol) showed the highest binding affinity with AKT1. These results suggest that Brassica rapa may play a role in regulating several pathways that are involved in the development of Diabetes Mellitus.
 Keywords: Network pharmacology, molecular mechanisms, Brassica rapa, Diabetes Mellitus (DM)