ArticleChinese medicine2024
Si-Wu-Tang alleviates metabolic dysfunction-associated fatty liver disease by inhibiting ACSL4-mediated arachidonic acid metabolism and ferroptosis in MCD diet-fed mice.
Article in Chinese medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed.
- Homo- and hetero-dimeric sesquiterpenoids with unprecedented skeletons and their co-occurring monomers from Vernonia solanifolia with anti-liver steatotic potential.Chinese medicine · 2026Article
- Si-Wu-Tang Targets Microbiota Homeostasis and Intestinal Mucosal Barriers to Provide Protection Against MASLD by FavoringPharmaceuticals (Basel, Switzerland) · 2026Article
- SIRT1-mediated FABP4 destabilization attenuates fibrosis and ferroptosis in non-alcoholic fatty liver disease.Clinical and experimental medicine · 2026Article
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Tao-Hong-Si-Wu-Tang protects against methionine- and choline-deficient diet-induced hepatic steatosis in rats and is associated with inhibition of oxidative stress, inflammation, apoptosis, and pyroptosis.Frontiers in immunology · 2026Article
- Ferroptosis: A Novel Mechanism and Therapeutic Target of Traditional Chinese Medicine for Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of inflammation research · 2026Review
- ACSL4-Mediated Ferroptosis and its Biological Functions and Potential Therapeutic Significance in Liver Diseases.Current pharmaceutical design · 2026Review
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Abstract
backgroundMetabolic 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.
methodsFirst, 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.
resultsSerological 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.
conclusionIn 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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