NETWORK PHARMACOLOGY AND MOLECULAR DYNAMIC EVALUATION OF MYCELIA -DERIVED QUINOLINE AGAINST NON-ALCOHOLIC FATTY LIVER DISEASE

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is a progressive metabolic disorder associated with hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis. Due to the limited availability of effective pharmacological therapies, exploration of novel bioactive compounds with multi-target therapeutic potential has become increasingly important[1]. In the present study, an integrated computational approach involving Gas Chromatography–Mass Spectrometry (GC–MS), network pharmacology, molecular docking, and molecular dynamics (MD) simulation was employed to investigate the therapeutic potential of quinoline-associated heterocyclic compounds identified from the mycelial extracts of Ganoderma lucidum and Hericium erinaceus against NAFLD.

GC–MS analysis revealed the presence of quinoline and its derivatives, indicating the occurrence of alkaloid-like bioactive metabolites. Network pharmacology analysis identified 69 overlapping targets associated with inflammatory and metabolic pathways involved in NAFLD progression. Gene Ontology and KEGG pathway enrichment analyses demonstrated significant involvement of TNF signaling, oxidative stress response, and lipid metabolism pathways. Molecular docking analysis showed favorable interaction between quinoline and TNF-α protein (PDB ID: 2AZ5), with a binding affinity score of −5.9 kcal/mol. Furthermore, MD simulation confirmed the structural stability of the quinoline–TNF-α complex through stable RMSD, RMSF, Rg, SASA, PCA, and FEL profiles. Overall, the findings suggest that quinoline-associated heterocyclic compounds may serve as promising therapeutic candidates against NAFLD.