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Abstract：
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear.
METHODS: First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients.
RESULTS: Serological and hepatic histopathological findings indicated SWT\'s discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD.
CONCLUSIONS: In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications.
METHODS: First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients.
RESULTS: Serological and hepatic histopathological findings indicated SWT\'s discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD.
CONCLUSIONS: In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications.
摘要：
背景：代谢功能障碍相关的脂肪性肝病（MAFLD）是世界范围内普遍存在的慢性肝病。四武堂(SWT)，中药汤剂对各种肝病有治疗作用。然而,SWT对MAFLD的保肝作用和潜在机制尚不清楚.
方法：首先，使用蛋氨酸-胆碱缺乏(MCD)饮食喂养小鼠模型,并进行脂质组学分析和转录组学分析.总铁离子的含量，亚铁离子，并检测脂质过氧化并进行普鲁士蓝染色以确认SWT对铁性凋亡的保护作用。最后,采用化学表征和网络药理学分析来鉴定潜在的活性成分。
结果：血清学和肝组织病理学发现表明SWT对MCD饮食诱导的MAFLD具有明显的治疗作用。脂质组学分析显示，SWT通过抑制TG合成和促进TG转运来改善肝内脂质积累。转录组分析表明，SWT通过抑制FA合成和促进FAβ-氧化来改善异常的FA代谢。然后，肥亡表型实验表明，SWT能有效阻止肝细胞的肥亡，它是由长链酰基辅酶A合成酶4（ACSL4）介导的花生四烯酸（AA）酯化诱导的。最后,化学表征和网络药理学分析确定，芍药苷和其他活性成分可能负责对抗铁凋亡和MAFLD的调节作用。
结论：结论：我们的研究揭示了复杂的机制，通过SWT改善MCD饮食诱导的MAFLD通过靶向FA代谢和铁凋亡在肝细胞，从而为MAFLD及其并发症的治疗提供了一种新的治疗方法。
方法：首先，使用蛋氨酸-胆碱缺乏(MCD)饮食喂养小鼠模型,并进行脂质组学分析和转录组学分析.总铁离子的含量，亚铁离子，并检测脂质过氧化并进行普鲁士蓝染色以确认SWT对铁性凋亡的保护作用。最后,采用化学表征和网络药理学分析来鉴定潜在的活性成分。
结果：血清学和肝组织病理学发现表明SWT对MCD饮食诱导的MAFLD具有明显的治疗作用。脂质组学分析显示，SWT通过抑制TG合成和促进TG转运来改善肝内脂质积累。转录组分析表明，SWT通过抑制FA合成和促进FAβ-氧化来改善异常的FA代谢。然后，肥亡表型实验表明，SWT能有效阻止肝细胞的肥亡，它是由长链酰基辅酶A合成酶4（ACSL4）介导的花生四烯酸（AA）酯化诱导的。最后,化学表征和网络药理学分析确定，芍药苷和其他活性成分可能负责对抗铁凋亡和MAFLD的调节作用。
结论：结论：我们的研究揭示了复杂的机制，通过SWT改善MCD饮食诱导的MAFLD通过靶向FA代谢和铁凋亡在肝细胞，从而为MAFLD及其并发症的治疗提供了一种新的治疗方法。
