Network pharmacological analysis on the mechanism of Linggui Zhugan decoction for nonalcoholic fatty liver disease.

Abstract

Nonalcoholic fatty liver disease (NAFLD), represents a chronic progressive disease that imposes a significant burden on patients and the healthcare system. Linggui Zhugan decoction (LGZGD) plays a substantial role in treating NAFLD, but its exact molecular mechanism is unknown. Using network pharmacology, this study aimed to investigate the mechanism of action of LGZGD in treating NAFLD. Active ingredients and targets were identified through the integration of data from the TCMSP, GEO, GeneCards, and OMIM databases. Cytoscape 3.9.1 software, in conjunction with the STRING platform, was employed to construct network diagrams and screen core targets. The enrichment analysis of gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways were conducted by using the R. Molecular docking of the active ingredients and core targets was performed with AutoDock Vina software. We obtained 93 and 112 active ingredients and potential targets using the bioinformatic analysis of LGZGD in treating NAFLD. The primary ingredients of LGZGD included quercetin, kaempferol, and naringenin. The core targets were identified AKT1, MYC, HSP90AA1, HIF1A, ESR1, TP53, and STAT3. Gene ontology function enrichment analysis revealed associations with responses to nutrient and oxygen levels, nuclear receptor activity, and ligand-activated transcription factor activity. Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis implicated the involvement of the PI3K-Akt, IL-17, TNF, Th17 cell differentiation, HIF-1, and TLR signaling pathways. Molecular docking studies indicated strong binding affinities between active ingredients and targets. LGZGD intervenes in NAFLD through a multi-ingredient, multi-target, and multi-pathway approach. Treatment with LGZGD can improve insulin resistance, oxidative stress, inflammation, and lipid metabolism associated with NAFLD.