Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health burden with limited therapeutic options. Cinnamomum cassia, a medicinal-food homologous plant, contains principal bioactive cinnamaldehyde (CA), whose anti-MASLD mechanisms require clarification. This study employed both a high-fat diet (HFD)-induced MASLD model and a free fatty acid (FFA)-stimulated cell model. CA administration attenuated intracellular lipid accumulation in vitro and ameliorated both hepatic steatosis and systemic hyperlipidemia in vivo, while inhibiting hepatic lipid peroxidation. Mechanistically, integrated RNA-seq, network pharmacology, siRNA, immunofluorescence, and transmission electron microscopy analyses identified the SIRT1/FOXO1–autophagy axis as CA’s key regulatory pathway. Gut microbiome profiling revealed CA’s capacity to ameliorate HFD-induced dysbiosis, particularly enriching Lachnospiraceae_NK4A136. Fecal microbiota transplantation (FMT) and Spearman correlations link serum lipids and hepatic injury factors to gut microbiota, indicating partially microbiota-mediated metabolic modulation by CA. Collectively, CA ameliorates MASLD through coordinated autophagy enhancement and microbial homeostasis restoration, holding promise as a functional food ingredient for metabolic liver disease prevention.
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Data availability
The datasets generated and/or analyzed during the current study are not publicly available due to the fact that related research is still in progress, but are available from the corresponding author on reasonable request. The raw data and metadata are maintained on the Majorbio cloud platform (www.majorbio.com), where the omics sequencing was performed.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (82304831), Henan Science Fund for Excellent Young Scholars (242300421090), China Postdoctoral Science Foundation (2023TQ0109 and GZB20230196), Associates Fund of Henan Province science and technology research and development program (232301420077), Young Talent Support Program of Henan Association for Science and Technology (2025HYTP092), and National Administration of Traditional Chinese Medicine Key Discipline Construction Project of High-Level TCM (ZYYZDXK-2023005). We also gratefully acknowledge the Central Plains Science and Technology Innovation Young Top Talent Project (2024) for financial support.
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X.R. Wang: Writing—original draft, visualization, methodology, and data curation, and conceptualization. Y.G. Song and W.Y. Zhao: Methodology, data curation, and formal analysis. Y.T. Liu: Methodology, data curation, and formal analysis. Y.P. Fu: Methodology. Y. Zhang: Methodology. Quanyou Zhao: Methodology. W.X. Zhao, M.S. Miao, and X.B. Wang: Project administration, writing—review and editing, and funding acquisition. Z.Z. Li: Writing—review and editing, data curation, visualization, project administration, conceptualization, and funding acquisition.
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Wang, X., Song, Y., Zhao, W. et al. Cinnamaldehyde mitigates MASLD through SIRT1/FOXO1-induced autophagy and synergistic gut microbiota modulation. npj Sci Food (2026). https://doi.org/10.1038/s41538-026-00815-6
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DOI: https://doi.org/10.1038/s41538-026-00815-6
