Elucidating the molecular mechanisms underlying anti-inflammatory effects of Morchella esculenta in the arachidonic acid metabolic pathway by network pharmacology and molecular docking

Abstract

AbstractMorchella esculenta is an edible fungus with a uniquely delicious flavor and remarkable benefits for health. Herein, the molecular mechanism underlying the anti-inflammatory effects of Morchella esculenta was elucidated using molecular docking and network pharmacology. NPASS, Super-pred, SEA, Swiss Target Prediction, GeneCards, DisGeNET, Omim database, and STRING platform were used to select anti-inflammatory targets and construct target protein interaction networks using the active ingredients of Morchella esculenta. The OmicShare cloud platform was used to analyze GO functions and KEGG pathways related to the target, and the AutoDock Vina software was used to perform molecular docking and molecular dynamics (MD) simulation on the main target. Based on Cytoscape’s “Network Analysis”, the degree was used to identify potential key targets, and different inflammatory transcriptome data sets were used to evaluate core targets showing clinical significance. The active ingredient of Morchella esculenta identified from the NPASS database was EOYA, which had 43 anti-inflammatory targets, including NR1I2, PTGS1, PTGS2, CYP4F2, CYP3A4, TLR4, MAPK1, PLA2G4A, and PTPN11, and was mainly implicated in arachidonic acid metabolism, vascular endothelial growth factor signal pathway, and sphingomyelin signal transduction pathway, indicating that the anti-inflammatory effects of EOYA were mainly related to these biological processes. The degree was used to select 9 potential effective targets, namely NR1I2, PTGS1, PTGS2, CYP4F2, CYP3A4, TLR4, MAPK1, PLA2G4A, and PTPN11, among which NR1I2, PTGS1, PTGS2, PLA2G4A, MAPK1, CYP3A4, and TLR4 showed clinical significance. Molecular docking results showed that (E)-Octadec-11-En-9-Ynoic Acid (EOYA) could spontaneously bind to the 9 core targets, and the binding fractions of NR1I2, PTGS1, PTGS2, CYP4F2, and CYP3A4 were the highest. The MD simulation results showed that EYOA did indeed bind well NR1I2 to PTGS2, and the complex has high stability. Morchella esculenta can regulate the activity of prostaglandin endoperoxide synthetase, and affect the biosynthesis of prostaglandins, thereby impacting the metabolic pathway of arachidonic acid.