[Mechanism of Arisaema Cum Bile in treating hyperlipidemia in rats based on lipidomics]

This study investigated the underlying mechanisms of lipid-lowering effect of Arisaema Cum Bile by using lipidomics technology. The hyperlipidemia rat model was established through feeding a high-fat diet continuously for 4 weeks. The rats were randomized into five groups after the successful modeling: model control, fenofibrate(40 mg·kg~(-1)), high-dose Arisaema Cum Bile(2.8 g·kg~(-1)), medium-dose Arisaema Cum Bile(1.4 g·kg~(-1)), and low-dose Arisaema Cum Bile(0.7 g·kg~(-1)). After the drug intervention for four consecutive weeks, serum samples were collected for blood lipid parameter and liver function determination. Hepatic lipid change was detected using UPLC-Q-TRAP-MS/MS, with metabolic pathways analyzed via the Kyoto Encyclopedia of Genes and Genomes(KEGG) database. The potential lipid-lowering pathways and targets of Arisaema Cum Bile were explored through immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay, and qRT-PCR. The results demonstrated that Arisaema Cum Bile can significantly improve the blood lipid indicators and liver function indexes in rats with hyperlipidemia, and the high-dose Arisaema Cum Bile treatment exhibited superior lipid-lowering efficacy compared to treatment at other doses. Additionally, 44 differentially expressed lipids were identified in hyperlipidemia rats through lipidomics analysis after the high-dose Arisaema Cum Bile intervention, mainly including carnitines, lysophosphatidic acids, phosphatidic acids, phosphatidylethanolamines, phosphatidylglycerols, and triglycerides. Glycerophospholipid(GP) metabolism was regarded as the most contributing pathway according to KEGG pathway enrichment analysis. Finally, the integrative analysis of results from molecular biology experiments indicated that Arisaema Cum Bile exerted a significant lipid-lowering effect primarily through activating peroxisome proliferator-activated receptor(PPAR) pathway, suppressing lipid/cholesterol biosynthesis, promoting lipid/cholesterol metabolism and enhancing their transport, and modulating systemic lipid metabolism process.