Combination of Metabolomics, Lipidomics, and Molecular Biology for the Investigation of the Metabolic Disturbance of Short-Term Administration of Emodin.

Emodin, a natural anthraquinone derivative, is an active ingredient in many Chinese traditional herbs. Interestingly, although it is generally considered to possess hepatoprotective activity, some studies have also reported that it has a certain degree of hepatotoxicity. Additionally, the underlying metabolic regulation of emodin remains uncertain. Therefore, we conducted a nontargeted metabolomic study based on UHPLC/Q-Orbitrap-MS and NMR. Data are available via ProteomeXchange with the identifier PXD055000. The results indicated a close association between the short-term administration of emodin and lipid metabolism. Moreover, a lipidomics investigation utilizing QTRAP 6500 + UHPLC-MS/MS was conducted, with a focus on determining the position of C═C double bonds in unsaturated lipids based on Paternò-Büchi (PB) reaction to discover the metabolic disturbance more precisely. Specifically, lipidomics revealed elevated levels of free fatty acids (FFA) alongside notable reductions in sphingomyelin (SM) and triacylglycerol (TAG) levels. Furthermore, the combination of PB reaction and molecular biology results indicated that short-term administration of emodin may lead to the accumulation of n-6 polyunsaturated fatty acids by up-regulating the expression of FASN, stearyl CoA desaturase 1 (SCD1), and cytosolic phospholipase A 2 (cPLA2). Simultaneously, up-regulation of cyclooxygenase-2 (Cox-2) expression was observed, potentially fostering the production of prostaglandin E2 (PGE2) and subsequent inflammation.