Approaches Based on Network Pharmacology and Molecular Docking to Predict the Molecular Mechanism of Plumbago zeylanicas Anti-Inflammatory Action

Abstract

Background: The roots of Plumbago zeylanica (P. zeylanica) are widely utilized in the traditional medicine system, i.e., Ayurveda for the treatment of piles, inflammatory diseases, intestinal disorders, abdominal pain, and inflammation of the rectum. Previous experimental studies revealed the anti-inflammatory and antiarthritic activities of P. zeylanica. Because of the experimental and clinical effectiveness of the roots of P. zeylanica root in painful inflammatory conditions and rheumatic diseases, this study aimed to evaluate the network pharmacology to predict the phytoconstituents and signaling pathways of the antiarthritic effect of P. zeylanica. Methods: As per the first step in the network pharmacology analysis, the phytoconstituents were retrieved from the relevant database, and the drug targets as well as the disease targets were downloaded, from the relevant databases. From there, the common targets were obtained, and then, Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis to predict the pathways/processes by which these targets are involved in rheumatoid arthritis (RA). Further, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADME/T), molecular docking, and dynamics studies of the resultant bioactive compounds of P. zeylanica with the regulated proteins were evaluated. Results: At first, using the network pharmacology analysis, the key target proteins in RA were predicted, then the key pathways were predicted using PPI, GO, and KEGG enrichment analysis in the treatment effects of P. zeylanica on RA. These key pathways used to be the responses to oxygen-containing compounds, organic response, and cellular response to a chemical stimulus which are synchronized by cancer, Phosphoinositide 3-kinases/Ak strain transforming (PI3K/AKT) signaling, lipid and atherosclerosis, microRNAs in cancer, calcium signaling and fluid shear stress and atherosclerosis pathways which indicates the involvement of abnormal proliferation of the immune cells and inflammation which are the characteristic features of rheumatoid arthritis. Further, the molecular docking, dynamics, Induced Fit Docking (IFD), and ADME/T studies revealed that the bioactive ingredients of P. zeylanica strongly bind with the essential target proteins in the ambience of rheumatoid arthritis. Conclusion: Hence, this study revealed computationally predicted the key targets of P. zeylanica phytoconstituents specific to its anti-inflammatory action in alleviating rheumatoid arthritis.