Combination of\nMetabolomics, Lipidomics, and Molecular\nBiology for the Investigation of the Metabolic Disturbance of Short-Term\nAdministration of Emodin

Emodin,\na natural anthraquinone derivative, is an active ingredient\nin many Chinese traditional herbs. Interestingly, although it is generally\nconsidered to possess hepatoprotective activity, some studies have\nalso reported that it has a certain degree of hepatotoxicity. Additionally,\nthe underlying metabolic regulation of emodin remains uncertain. Therefore,\nwe conducted a nontargeted metabolomic study based on UHPLC/Q-Orbitrap-MS\nand NMR. Data are available via ProteomeXchange with the identifier\nPXD055000. The results indicated a close association between the short-term\nadministration of emodin and lipid metabolism. Moreover, a lipidomics\ninvestigation utilizing QTRAP 6500<sup>+</sup> UHPLC-MS/MS was conducted,\nwith a focus on determining the position of CC double bonds\nin unsaturated lipids based on Paternò–Büchi\n(PB) reaction to discover the metabolic disturbance more precisely.\nSpecifically, lipidomics revealed elevated levels of free fatty acids\n(FFA) alongside notable reductions in sphingomyelin (SM) and triacylglycerol\n(TAG) levels. Furthermore, the combination of PB reaction and molecular\nbiology results indicated that short-term administration of emodin\nmay lead to the accumulation of n-6 polyunsaturated fatty acids by\nup-regulating the expression of FASN, stearyl CoA desaturase 1 (SCD1),\nand cytosolic phospholipase A 2 (cPLA2). Simultaneously, up-regulation\nof cyclooxygenase-2 (Cox-2) expression was observed, potentially fostering\nthe production of prostaglandin E2 (PGE2) and subsequent inflammation.