Abstract: To systematically explore the mechanism underpinning the influence of combination of Lu’an Guapian tea, Cassiae Semen and Lycium barbarum on glycolipid metabolism, this study initially identified 32 core functional targets associated with metabolic dysfunction-associated steatotic liver disease (MASLD) for these three ingredients using the TCMSP, PharmMapper, and GeneCards databases. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database, which revealed significant enrichment of these targets in pathways such as diabetic cardiomyopathy, lipid and atherosclerosis, and insulin resistance (IR). A “drug-component-target-pathway” four-dimensional network was further constructed and analyzed topologically. The findings suggested that epigallocatechin gallate and epigallocatechin may be the principal active compounds responsible for ameliorating MASLD. Additionally, molecular docking analyses revealed that these active constituents interacted with key targets (insulin receptor (INSR), AKT serine/threonine kinase 1 (AKT1), glycogen synthase kinase-3 beta (GSK3β), protein tyrosine phosphatase non-receptor type 1 (PTPN1)) in the IR signaling pathway primarily through hydrogen bonding and hydrophobic interactions. A HepG2 cell model of IR was employed to assess the hypoglycemic and lipid-lowering effects of combinations at different ratios. The results indicated that combination of Lu’an Guapian tea, Cassiae Semen, and L. barbarum at 1:1:2 exhibited the most significant hypoglycemic activity, whereas their 2:1:1 combination showed the best lipid-lowering efficacy. This study provides a theoretical foundation for the development of functional plant-based formulations.

Key words: Lu’an Guapian tea; Cassiae Semen; Lycium barbarum; metabolic dysfunction-associated steatotic liver disease; insulin resistance; glucose and lipid metabolism