Abstract This study aimed to investigate the mechanism of action of Sophora Flos (SF) in the treatment of hyperlipidemia (HLP) using network pharmacology and molecular docking methods, and to optimize the extraction process of the predicted active components. The STRING database was used for protein interaction analysis and PPI network construction via Cytoscape 3.9.1. Pymol was employed for docking and visualization. An extensive review of SF identified 6 active ingredients, 297 related objectives, 84 disease objectives, and 57 total objectives. After protein interaction and topology analysis, 18 core targets were identifi ed. These included 146 gene function entries (P < 0.05). Active compounds, mainly flavonoids, can modulate the expression of various proteins such as TNF, IL-6, IL-1β, PPARG, and TGFB1 to achieve therapeutic effects on HLP. The network pharmacology and molecular docking results suggested that the active flavonoids component in SF may be related to the treatment of hyperlipidemia. Therefore, the orthogonal experiment method was used to optimize the extraction process of total flavonoid from SF using ethanol reflux extraction, based on a single factor experiment. The effects of reflux time, solid-liquid ratio, ethanol concentration, and other factors on the extraction of total flavonoid from SF were investigated. The optimum process conditions were reflux time of 1.25 h, solid-liquid ratio of 1:15 g/mL and ethanol concentration of 60%. Using these conditions, the purity of total flavonoid extracted from SF was 70.33 ± 0.22%.
