The mechanism of 6-gingerol in improving glycolipid metabolism disorders was investigated by network pharmacology and confirmed by L6 cells cultured with high fructose and high oleic acid.Using TCMSP database,SwissTargetPrediction database and GeneCards database,the targets of 6-gingerol on glycolipid metabolism disorder were obtained,Cytoscape 3.7.1 was used to construct the relationship between compound target and disease network,protein-protein interaction (PPI) was analyzed using STRING database,GO functional enrichment and KEGG pathway enrichment through R packet,and gene mapping was carried out by KEGG Mapper.Combined with GO enrichment analysis,KEGG pathway analysis and gene mapping results,this study selected the PI3K-AKT-mTOR axis,NF-κB-p65 and ERK in vitro.The model of glycolipid metabolism disorder in L6 cells were established by high fructose and high oleic acid.TG and oil red staining were used to assess lipid deposition level and Western blot was used to detect the expression of inflammatory factors IL-1β and TNF-α.RT-PCR and western blot were used to detect the levels of mRNA and protein associated with PI3K-AKT- mTOR,NF-κB-p65 and ERK.A total of 113 targets for 6-gingerol treatment of glucolipid metabolism disorders were identified by network pharmacologic analysis.GO enrichment analysis showed that 6-gingerol was closely related to protein kinase activity.A total of 20 KEGG signaling pathways were screened including PI3K-AKT signaling pathway,hepatitis B,hepatitis C,human cytomegalovirus infection,autophagy,etc. In vitro experiments showed that 6-gingerol could reduce lipid accumulation in L6 cells induced by high fructose and high oleic acid and the expression of pro-inflammatory factors IL-1β and TNF-α.Meanwhile,6-gingerol could up-regulate the expression of phosphorylation of AKT,and down-regulate the expression of phosphorylation of mTOR,NF-κB-p65 and ERK.In addition,6-gingerol could increase the expression of AKT at mRNA level.These results suggest that 6-gingerol can improve glucolipid metabolism disorder in L6 cells treated with high fructose and high oleic acid,and relate to activate PI3K-AKT-mTOR axis and inhibit inflammation through blocking phosphorylation of NF-κB-p65 and ERK.These findings provide theoretical basis for subsequent basic research.