The Effect of Viniferin on Liver Cancer: Research Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation

TL;DR

This study explores how viniferin, a natural compound, may work against liver cancer by analyzing its effects on key proteins and pathways.

Contribution

The study identifies viniferin as a multi-target agent for hepatocellular carcinoma through network pharmacology and molecular simulations.

Findings

Viniferin isomers ε- and δ-viniferin showed favorable drug-like properties and low hepatotoxicity.

Twenty-four hub genes, including AKT1 and HSP90AA1, were identified as key targets for viniferin in liver cancer.

Molecular simulations confirmed the stability of ε-viniferin binding to the APP protein.

Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) is a primary malignancy often driven by metabolic syndrome, fatty liver disease, and chronic hepatitis. These conditions foster a pro-inflammatory microenvironment that promotes tumor progression. Viniferin, a natural oligostilbene, has gained attention for its potential bioactivity. This study utilized an in silico network pharmacology approach to elucidate the pharmacokinetic properties and molecular mechanisms of ε- and δ-viniferin against HCC within the context of metabolic and inflammatory liver pathologies. Methods: ADMET profiles were characterized using SwissADME and pkCSM. Therapeutic targets were identified by intersecting viniferin-associated molecules with disease genes from GeneCards. A protein–protein interaction (PPI) network was constructed, supplemented by GO and KEGG enrichment analyses. Molecular docking and 200 ns of molecular dynamics (MD) simulations evaluated the binding affinity and structural stability between viniferin isomers and identified hub proteins. Results: Both ε- and δ-viniferin showed favorable drug-like properties, including high gastrointestinal absorption and low hepatotoxicity. We identified 247 overlapping targets, with network analysis highlighting ten essential hub genes, including AKT1, HSP90AA1, ESR1, HIF1A, NFKB1, GSK3B, PTGS2, APP, MTOR, and PIK3CA. Enrichment analysis confirmed their involvement in critical oncogenic pathways. Molecular docking showed strong interactions with APP, HSP90AA1, and AKT1, while MD simulations validated the long-term stability of ε-viniferin within the APP binding pocket. Conclusions: These findings provide mechanistic insights into viniferin as a multi-target agent for HCC, justifying further experimental validation in pre-clinical models.

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