Effect of oridonin on oxylipins in the livers of mice with acute liver injury induced by D-galactosamine and lipopolysaccharide. 2022

Zhikun Zhan, and Tao Zhang, and Fahong Dai, and Xin Wen, and Yulian Chen, and Huanguo Jiang, and Tanwei Gu, and Yuan Cheng, and Lan Tang
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

OBJECTIVE Oridonin (Ori) has been shown to protect against acute liver injury (ALI) induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS). Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) and are key proinflammatory mediators. This study aimed to investigate the changes in oxylipins in the livers of mice with D-GalN/LPS-induced ALI and the effects of Ori on these changes. RESULTS 54 oxylipins in liver tissues were identified and qualitatively and quantitatively analyzed by ultra-performance liquid chromatography-electrospray ionization triple quadrupole mass spectrometry (UPLC-QTRAP/MS/MS). The levels of 12-HETE, 12-HEPE, 14(S)-HDHA, PGE2, dihomo-γ-linolenic acid and 13-HOTrE in the liver were significantly increased in the D-GalN/LPS-induced ALI group compared with the control group, and the levels of EPA and 7-HDHA were significantly decreased. However, pretreatment with Ori dramatically decreased the levels of 12-HETE, 12-HEPE, 14(S)-HDHA, PGE2 and 13-HOTrE compared with those of the ALI group and induced 7-HDHA and 15-oxoETE. Moreover, Ori reduced the protein levels of COX-1, COX-2, ALOX5, ALOX12 and ALOX15 induced by D-GalN/LPS, indicating that Ori altered oxylipins through the COX and LOX pathways. CONCLUSIONS These results suggest that the protective effect of Ori on ALI is partly mediated by affecting the oxylipin pathway.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D005688 Galactosamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001092 Arachidonate 12-Lipoxygenase An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in PLATELETS. 12-Lipoxygenase,Arachidonic Acid 12-Lipoxygenase,12 Lipoxygenase,12-Lipoxygenase, Arachidonate,12-Lipoxygenase, Arachidonic Acid,Arachidonate 12 Lipoxygenase,Arachidonic Acid 12 Lipoxygenase
D001093 Arachidonate 15-Lipoxygenase An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy-5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in NEUTROPHILS and LYMPHOCYTES. 15-Lipoxygenase,Arachidonic Acid 15-Lipoxygenase,15 Lipoxygenase,15-Lipoxygenase, Arachidonate,15-Lipoxygenase, Arachidonic Acid,Arachidonate 15 Lipoxygenase,Arachidonic Acid 15 Lipoxygenase
D001094 Arachidonate 5-Lipoxygenase An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes. 5-Lipoxygenase,Arachidonic Acid 5-Lipoxygenase,LTA4 Synthase,Leukotriene A Synthase,Leukotriene A4 Synthase,Leukotriene A4 Synthetase,5 Lipoxygenase,5-Lipoxygenase, Arachidonate,5-Lipoxygenase, Arachidonic Acid,Arachidonate 5 Lipoxygenase,Arachidonic Acid 5 Lipoxygenase,Synthase, LTA4,Synthase, Leukotriene A,Synthase, Leukotriene A4,Synthetase, Leukotriene A4

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