Network Pharmacology and Molecular Docking-Based Investigation of Tectoquinone Against Non-Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disorder associated with hepatic lipid accumulation, oxidative stress, inflammation and altered cellular signaling. Tectoquinone, a naturally occurring phytoconstituent, may possess potential activity against these pathological processes; however, its molecular mechanism in NAFLD remains insufficiently explored.

Objective: The present study aimed to identify potential targets and signaling pathways of tectoquinone associated with NAFLD and to evaluate its interaction with key hub proteins using molecular docking.

Methods: SwissADME was used to evaluate the physicochemical and drug-likeness properties of tectoquinone, while ProTox-3.0 was employed for toxicity prediction. Potential drug targets were obtained from SwissTargetPrediction, and NAFLD-associated targets were retrieved from GeneCards. Venny analysis identified 44 common targets between tectoquinone and NAFLD. Gene Ontology and KEGG pathway enrichment analyses were performed, followed by construction of a drug–pathway–gene network using Cytoscape. Network analysis identified five major hub targets: ESR1, CTNNB1, BCL2, NFE2L2 and GSK3B. Molecular docking was subsequently performed with selected hub proteins.

Results: Tectoquinone showed favorable drug-likeness characteristics and high gastrointestinal absorption, with no major toxicity predicted in the evaluated ProTox endpoints. Enrichment analysis indicated involvement of multiple pathways related to metabolic regulation, lipid metabolism, inflammation and cellular signaling. Molecular docking demonstrated binding affinities of −10.0 kcal/mol with BCL2, −6.9 kcal/mol with CTNNB1, and approximately 0.0 kcal/mol with ESR1. Among the evaluated proteins, BCL2 exhibited the strongest predicted binding affinity (−10.0 kcal/mol).

Conclusion: These findings suggest that tectoquinone may interact with multiple NAFLD-associated targets, with BCL2 emerging as the most promising docked target, warranting further experimental validation.