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LC-MRM-MS 法研究莪术酮对非酒精性脂肪性肝炎小鼠甘油磷脂代谢的伪靶向脂质组学分析。

Pseudotargeted lipidomics analysis of scoparone on glycerophospholipid metabolism in non-alcoholic steatohepatitis mice by LC-MRM-MS.

机构信息

College of Traditional Chinese Medicine, Hebei University, Baoding, Hebei, China.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

PeerJ. 2024 May 21;12:e17380. doi: 10.7717/peerj.17380. eCollection 2024.

DOI:10.7717/peerj.17380
PMID:38799063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11122033/
Abstract

As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of glycerophospholipid metabolism. Scoparone is the major bioactive component in which has been widely used to treat NASH in traditional Chinese medicine. However, the underlying mechanisms of scoparone against NASH are not yet fully understood, which hinders the development of effective therapeutic agents for NASH. Given the crucial role of glycerophospholipid metabolism in NASH progression, this study aimed to characterize the differential expression of glycerophospholipids that is responsible for scoparone's pharmacological effects and assess its efficacy against NASH. Liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) was performed to get the concentrations of glycerophospholipids, clarify mechanisms of disease, and highlight insights into drug discovery. Additionally, pathologic findings also presented consistent changes in high-fat diet-induced NASH model, and after scoparone treatment, both the levels of glycerophospholipids and histopathology were similar to normal levels, indicating a beneficial effect during the observation time. Altogether, these results refined the insights on the mechanisms of scoparone against NASH and suggested a route to relieve NASH with glycerophospholipid metabolism. In addition, the current work demonstrated that a pseudotargeted lipidomic platform provided a novel insight into the potential mechanism of scoparone action.

摘要

作为非酒精性脂肪性肝病(NAFLD)的炎症亚型,非酒精性脂肪性肝炎(NASH)的进展与甘油磷脂代谢紊乱有关。茵陈二酮是其中的主要生物活性成分,在中药中被广泛用于治疗 NASH。然而,茵陈二酮治疗 NASH 的潜在机制尚不完全清楚,这阻碍了 NASH 有效治疗药物的开发。鉴于甘油磷脂代谢在 NASH 进展中的关键作用,本研究旨在表征负责茵陈二酮药理作用的甘油磷脂的差异表达,并评估其对 NASH 的疗效。采用液相色谱-多重反应监测-质谱(LC-MRM-MS)测定甘油磷脂的浓度,阐明疾病机制,并深入了解药物发现。此外,高脂饮食诱导的 NASH 模型中的病理发现也呈现出一致的变化,茵陈二酮治疗后,甘油磷脂水平和组织病理学均恢复正常水平,表明在观察期间具有有益作用。总之,这些结果深化了对茵陈二酮治疗 NASH 机制的认识,并为通过甘油磷脂代谢缓解 NASH 提供了一种途径。此外,本工作表明,伪靶向脂质组学平台为茵陈二酮作用的潜在机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/0f4461adebf5/peerj-12-17380-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/48c51a2b575c/peerj-12-17380-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/eeb5895ec22f/peerj-12-17380-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/c1c526fef3ab/peerj-12-17380-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/6a37cfd8798d/peerj-12-17380-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/022bcaa43f8a/peerj-12-17380-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/0f4461adebf5/peerj-12-17380-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/48c51a2b575c/peerj-12-17380-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/eeb5895ec22f/peerj-12-17380-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/c1c526fef3ab/peerj-12-17380-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/6a37cfd8798d/peerj-12-17380-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/022bcaa43f8a/peerj-12-17380-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b2f/11122033/0f4461adebf5/peerj-12-17380-g006.jpg

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本文引用的文献

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J Org Chem. 2023 Aug 4;88(15):11253-11257. doi: 10.1021/acs.joc.2c02096. Epub 2022 Nov 30.
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Breakthroughs in therapies for NASH and remaining challenges.NASH 治疗方面的突破和尚存的挑战。
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Lipidomics Revealed Alteration of the Sphingolipid Metabolism in the Liver of Nonalcoholic Steatohepatitis Mice Treated with Scoparone.脂质组学揭示了滨蒿内酯处理的非酒精性脂肪性肝炎小鼠肝脏中鞘脂代谢的改变。
ACS Omega. 2022 Apr 14;7(16):14121-14127. doi: 10.1021/acsomega.2c00693. eCollection 2022 Apr 26.
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Lipid alterations in chronic liver disease and liver cancer.慢性肝病和肝癌中的脂质改变。
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