Hyperlipidemia and hepatic steatosis affect over 75% of patients with type 2 diabetes, resulting in dyslipidemia in diabetes. Cyclocarya paliurus (Batal.) Ijinskaja (CP) leaf is a herbal tea which has long been consumed by the Chinese population, particularly people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic effect in rats [1], although the detailed mechanisms and active ingredients responsible for this hypolipidemic effect have not been elucidated yet. In this study, we investigated the beneficial effects of CP and predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and network pharmacology approaches. Our results demonstrated serum and hepatic total triglyceride (TG), total cholesterol (T-CHO), low-density lipoproteins (LDL) and high-density lipoproteins (HDL) levels, as well as 30 lipids including cholesterol ester (CE), diglyceride (DG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM) in CP-treated mice were improved in comparison with those of diabetic mice without treatment. In parallel, 14 constituents of CP were determined in mice serum after CP administration. Mechanistically, the network pharmacological analysis revealed the predicted targets ALOX12, APP, BCL2, CYP2C9, PTPN1 and linked lipidome targets. PLD2, PLA2G(s) and PI3K(s) families are potential markers to be responsible for the CP effect on diabetic dyslipidemia, based on association analysis of the change of lipid metabolites in diabetic mice and active ingredients absorbed in blood after CP administration. In conclusion, this study verifies the beneficial effects of CP on diabetic dyslipidemia, which are associated with reducing accumulation of hepatic lipid droplets and regulating circulatory lipids in diabetic mice, possibly through PI3K signaling and MAPK signaling pathways.
References:
1 Lin Z, Wu Z-F, Jiang C-H, Zhang Q-W, Ouyang S, Che C-T, Zhang J, Yin Z-Q. The chloroform extract of Cyclocarya paliurus attenuates high-fat diet induced non-alcoholic hepatic steatosis in Sprague Dawley rats. Phytomedicine 2016; 23: 1475–1483
