四物汤通过抑制 ACSL4 介导的花生四烯酸代谢和铁蛋白沉积,缓解 MCD 膳食小鼠代谢功能障碍相关性脂肪肝。

IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Chinese Medicine Pub Date : 2024-06-06 DOI:10.1186/s13020-024-00953-7
Xiaoyong Xue, Le Wang, Ruiyu Wu, Yufei Li, Runping Liu, Zhi Ma, Kexin Jia, Yinhao Zhang, Xiaojiaoyang Li
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引用次数: 0

摘要

背景:代谢功能障碍相关性脂肪肝(MAFLD)是一种全球流行的慢性肝病。四物汤(SWT)是一种传统中药煎剂,对多种肝病有治疗作用。然而,四物汤对 MAFLD 的保肝作用及其机制仍不清楚:方法:首先,采用蛋氨酸-胆碱缺乏(MCD)饮食喂养小鼠模型,并进行脂质体分析和转录组分析。方法:首先,采用蛋氨酸胆碱缺乏(MCD)饮食喂养小鼠模型,进行脂质组分析和转录组分析,检测总铁离子、亚铁离子和脂质过氧化物的含量,并进行普鲁士蓝染色,以证实 SWT 对铁变态反应的保护作用。最后,通过化学特性分析和网络药理学分析确定了潜在的活性成分:结果:血清学和肝组织病理学结果表明,SWT 对 MCD 饮食诱导的 MAFLD 有明显的治疗作用。脂质体分析表明,SWT 通过抑制 TG 合成和促进 TG 转运,改善了肝内脂质积累。转录组分析表明,SWT通过抑制FA合成和促进FAβ-氧化改善了FA代谢异常。然后,铁突变表型实验显示,SWT 能有效抑制肝细胞铁突变,而肝细胞铁突变是由长链酰基-CoA 合成酶 4(ACSL4)介导的花生四烯酸(AA)酯化诱导的。最后,通过化学特性分析和网络药理学分析发现,芍药苷和其他有效成分可能对铁变态反应和 MAFLD 具有调节作用:总之,我们的研究揭示了SWT通过靶向肝细胞中的FA代谢和铁变态反应改善MCD饮食诱导的MAFLD的复杂机制,从而为治疗MAFLD及其并发症提供了一种新的治疗方法。
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Si-Wu-Tang alleviates metabolic dysfunction-associated fatty liver disease by inhibiting ACSL4-mediated arachidonic acid metabolism and ferroptosis in MCD diet-fed mice.

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.

Conclusion: 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.

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来源期刊
Chinese Medicine
Chinese Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.90
自引率
4.10%
发文量
133
审稿时长
31 weeks
期刊介绍: Chinese Medicine is an open access, online journal publishing evidence-based, scientifically justified, and ethical research into all aspects of Chinese medicine. Areas of interest include recent advances in herbal medicine, clinical nutrition, clinical diagnosis, acupuncture, pharmaceutics, biomedical sciences, epidemiology, education, informatics, sociology, and psychology that are relevant and significant to Chinese medicine. Examples of research approaches include biomedical experimentation, high-throughput technology, clinical trials, systematic reviews, meta-analysis, sampled surveys, simulation, data curation, statistics, omics, translational medicine, and integrative methodologies. Chinese Medicine is a credible channel to communicate unbiased scientific data, information, and knowledge in Chinese medicine among researchers, clinicians, academics, and students in Chinese medicine and other scientific disciplines of medicine.
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