Lipidomic profiling of serum and liver tissue reveals hepatoprotective mechanism of taxifolin in rats with CCl4-induced subacute hepatic injury based on LC-MS/MS

Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from Pseudotsuga taxifolia, has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl₄ induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl₄, which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl₄, including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.