作为非酒精性脂肪性肝病(NAFLD)的炎性亚型,非酒精性脂肪性肝炎(NASH)的进展与甘油磷脂代谢紊乱有关.前言:黄芩酮是目前毛细蒿中主要的生物活性成分,已被广泛用于中药治疗NASH。然而,scoparone抗NASH的潜在机制尚未完全理解,这阻碍了NASH有效治疗剂的开发。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scoparone药理作用的甘油磷脂的差异表达,并评估其对NASH的疗效。进行液相色谱-多反应监测-质谱(LC-MRM-MS)以获得甘油磷脂的浓度,阐明疾病的机制,并强调对药物发现的见解。此外,病理结果在高脂饮食诱导的NASH模型中也表现出一致的变化,在soparone治疗后,甘油磷脂的水平和组织病理学与正常水平相似,表明在观察时间期间的有益效果。总之,这些结果完善了对scoparone抗NASH机制的认识,并提出了通过甘油磷脂代谢缓解NASH的途径.此外,目前的工作表明,一个伪靶向的脂质组学平台为scoparone作用的潜在机制提供了新的见解.
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 Artemisia capillaris 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.