Network pharmacology and molecular simulation study on the multi-target gene regulatory mechanism of Isatis indigotica against hepatic inflammation
TL;DR
It is suggested that Isatis indigotica acts on HBV-associated hepatic inflammation through multi-target synergistic regulation of NF-κB and JAK-STAT signaling pathways, providing mechanistic insights and potential therapeutic targets for HBV management.
Abstract
Isatis indigotica (Banlangen) is a classic Traditional Chinese Medicine herbal remedy with well-documented antiviral and anti-inflammatory properties. However, the molecular mechanisms underlying its therapeutic effects against hepatitis B virus (HBV)-associated hepatic inflammation remain incompletely understood. This study aimed to systematically elucidate the multi-target regulatory mechanisms of Isatis indigotica against HBV-associated hepatic inflammation using network pharmacology and molecular simulation approaches. Bioactive compounds were screened from the TCMSP database (OB ≥ 30%, oral bioavailability; DL ≥ 0.18, drug-likeness). Candidate targets were identified by integrating SwissTargetPrediction with GeneCards/OMIM disease targets. Protein-protein interaction (PPI) network topology analysis identified hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Metascape. Molecular docking and 100 ns all-atom molecular dynamics (MD) simulation were conducted to validate compound-target binding. Seventeen bioactive compounds were identified, yielding 1,023 compound targets. Intersecting with 1,676 HBV disease targets produced 142 candidate genes. PPI network analysis identified AKT1, IL6, TP53, and TNF as hub genes, significantly enriched in NF-κB, JAK-STAT, and TNF signaling pathways (P < 0.01). Molecular docking confirmed favorable binding affinities, with IQ (6-(3-oxoindolin-2-ylidene)indolo[2,1-b]quinazolin-12-one) showing optimal binding to AKT1 (ΔG = −9.35 kcal/mol). MD simulation verified stable binding over 100 ns. This network pharmacology study suggests that Isatis indigotica acts on HBV-associated hepatic inflammation through multi-target synergistic regulation of NF-κB and JAK-STAT signaling pathways, providing mechanistic insights and potential therapeutic targets for HBV management.