The potential of <i>Gynostemma pentaphyllum</i> in the treatment of hyperlipidemia and its interaction with the <scp>LOX1</scp>‐<scp>PI3K</scp>‐<scp>AKT</scp>‐<scp>eNOS</scp> pathway

<i>Gynostemma pentaphyllum</i>, a traditional Chinese medicine, is widely used to treat various diseases, but its therapeutic effects and mechanisms of action on hyperlipidemia remain unclear. This study aims to investigate the effects of Danshen leaf on hyperlipidemia through network pharmacology, molecular docking, and cellular experiments, elucidating its multifaceted mechanism of action within the LOX1-PI3K-AKT-eNOS pathway. First, the active ingredients and targets of <i>G. pentaphyllum</i> were screened using the Traditional Chinese Medicine Systems Pharmacology database. Then, targets for hyperlipidemia were identified using the OMIM and GeneCards databases, and potential therapeutic targets for <i>G. pentaphyllum</i> in treating hyperlipidemia were determined. An active ingredient-target network was constructed using Cytoscape software, and a protein-protein interaction (PPI) network was built and visualized using the STRING database and Cytoscape software. Finally, GO functional and KEGG pathway enrichment analyses were performed, and the predicted mechanisms were validated through molecular docking and cell experiments. 85 targets for <i>G. pentaphyllum</i> and 1556 for Hyperlipidemia were screened, with 53 common targets. Twenty-four active ingredients of <i>G. pentaphyllum</i> were found to be involved in the treatment of hyperlipidemia. Key nodes such as Rhamnazin, Isofucosterol, and quercetin, and targets NCOA2, NR3C2, PGR, and PPARG showed high relevance. In the PPI network, 8 nodes, including IL6, PPARG, and VEGFA, exhibited high centrality. GO functional and KEGG pathway enrichment analyses indicated that <i>G. pentaphyllum</i> may treat hyperlipidemia by influencing various biological functions and pathways, such as DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and lipid and atherosclerosis. Cell experiments demonstrated that <i>G. pentaphyllum</i> significantly regulated the expression of key proteins in the LOX1-PI3K-AKT-eNOS pathway, thereby improving hyperlipidemia. <i>G. pentaphyllum</i> improves hyperlipidemia by mediating the LOX1-PI3K-AKT-eNOS pathway. This study provides a new theoretical basis and experimental evidence for applying <i>G. pentaphyllum</i> to treating hyperlipidemia.