非酒精性脂肪肝病（NAFLD）已发展成为最常见的慢性肝病，并可导致肝癌。我们实验室此前开发了治疗NAFLD的新方“八折汤”（EZD），在临床中显示出良好的疗效。但其药效物质基础和机制尚未揭示。采用脂质组学、网络药理学和药代动力学相结合的策略揭示EZD抗NAFLD的活性成分和机制。组织病理学结果表明，EZD 减轻了非酒精性脂肪纤维化模型小鼠肝脏中胶原沉积和脂肪变性的程度。此外，以磷脂酶A2 IVA组（PLA2G4A）和细胞色素P450为核心目标，以12,13-顺式环氧十八烯酸、12(S)-羟基二十碳四烯酸、白三烯B4为核心靶标的甘油磷脂代谢、花生四烯酸代谢、甘油脂代谢和亚油酸代谢发现以前列腺素E2、磷脂酰胆碱（PC）和三酰甘油（TG）为主要脂质参与EZD治疗NAFLD。重要的是，柚皮素、青蒿素、canadine 和荷包牡丹碱被确定为 EZD 抗 NAFLD 的活性成分；特别是，柚皮素通过抑制 PLA2G4A 的表达来减少 PC 消耗，从而促进极低密度脂蛋白的充分合成，以在肝脏中运输过量的 TG。该研究为EZD在NAFLD中的应用提供了宝贵的数据和理论支持。© 2023 作者。

Nonalcoholic fatty liver disease (NAFLD) has developed into the most common chronic liver disease and can lead to liver cancer. Our laboratory previously developed a novel prescription for NAFLD, "Eight Zhes Decoction" (EZD), which has shown good curative effects in clinical practice. However, the pharmacodynamic material basis and mechanism have not yet been revealed. A strategy integrating lipidomics, network pharmacology and pharmacokinetics was used to reveal the active components and mechanisms of EZD against NAFLD. The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice. Furthermore, glycerophospholipid metabolism, arachidonic acid metabolism, glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA (PLA2G4A) and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid, 12(S)-hydroxyeicosatetraenoic acid, leukotriene B4, prostaglandin E2, phosphatidylcholines (PCs) and triacylglycerols (TGs) as the main lipids were found to be involved in the treatment of NAFLD by EZD. Importantly, naringenin, artemetin, canadine, and bicuculline were identified as the active ingredients of EZD against NAFLD; in particular, naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver. This research provides valuable data and theoretical support for the application of EZD against NAFLD.© 2023 The Authors.