Zhan Zhikun, Zhang Tao, Dai Fahong, Wen Xin, Chen Yulian, Jiang Huanguo, Gu Tanwei, Cheng Yuan, Tang Lan
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.
Department of Pharmaceutical, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 5101201 China.
Int Immunopharmacol. 2022 Jan;102:108387. doi: 10.1016/j.intimp.2021.108387. Epub 2021 Nov 24.
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.
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.
These results suggest that the protective effect of Ori on ALI is partly mediated by affecting the oxylipin pathway.
冬凌草甲素（Ori）已被证明可预防由D-半乳糖胺（D-GalN）和脂多糖（LPS）诱导的急性肝损伤（ALI）。氧化脂质是多不饱和脂肪酸（PUFA）的氧化产物，是关键的促炎介质。本研究旨在探讨D-GalN/LPS诱导的ALI小鼠肝脏中氧化脂质的变化以及Ori对这些变化的影响。
通过超高效液相色谱-电喷雾电离三重四极杆质谱（UPLC-QTRAP/MS/MS）对肝组织中的54种氧化脂质进行了鉴定、定性和定量分析。与对照组相比，D-GalN/LPS诱导的ALI组肝脏中12-HETE、12-HEPE、14(S)-HDHA、PGE2、二高-γ-亚麻酸和13-HOTrE的水平显著升高，而EPA和7-HDHA的水平显著降低。然而，与ALI组相比，Ori预处理显著降低了12-HETE、12-HEPE、14(S)-HDHA、PGE2和13-HOTrE的水平，并诱导了7-HDHA和15-氧代二十碳三烯酸的产生。此外，Ori降低了D-GalN/LPS诱导的COX-1、COX-2、ALOX5、ALOX12和ALOX15的蛋白水平，表明Ori通过COX和LOX途径改变了氧化脂质。
这些结果表明，Ori对ALI的保护作用部分是通过影响氧化脂质途径介导的。
