Abstract
To investigate the therapeutic effect of total flavones of Abelmoschus manihot (L.) Medic (TFA) on CCl4-induced liver fibrosis in mice, and to clarify the mechanism of action of TFA in ameliorating liver fibrosis by untargeted metabolomics and intestinal microbiota 16S rRNA sequencing, in order to provide an experimental basis for the clinical application of TFA in the treatment of liver fibrosis. To establish a mice model of CCl4-induced liver fibrosis, and liver injury was assessed through histopathology, liver function markers (ALT, AST), inflammatory cytokines, and oxidative stress indicators. Serum untargeted metabolomics was conducted via LC-MS/MS, and intestinal microbiota profiles were analyzed by 16S rRNA sequencing. TFA treatment significantly reduced ALT and AST levels by approximately 55% and 40%, respectively, and markedly ameliorated histopathological changes. It also attenuated oxidative stress and inflammation. Metabolomic analysis identified 83 differential metabolites, indicating that TFA restored disruptions in glycerophospholipid, tryptophan, and arachidonic acid metabolism. Gut microbiota sequencing showed that TFA increased beneficial bacteria and decreased harmful bacteria. Furthermore, TFA downregulated the expression of CYP1A1, CYP2E1, and ALOX15 in liver tissue, suggesting modulation of arachidonic acid metabolism. TFA alleviated CCl4-induced liver fibrosis in mice by reducing oxidative stress and inflammation, improving gut microbiota dysbiosis, and regulating host metabolism. These findings suggest that TFA may hold potential as a multi-target agent for liver fibrosis, although further studies are required to confirm its efficacy in other models and females.
Data availability
The data reported in this paper have been deposited in the OMIX, China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences (https://ngdc.cncb.ac.cn/omix: accession no.OMIX010404 and accession no.OMIX010405).
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Acknowledgements
Sequencing service and data analysis service were provided by Wekemo Tech Group Co., Ltd. Shenzhen China.
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Dengya Li drafted the manuscript. Emily Heya Tang performed the data processing. Yan Zhang, Shuying Song and Luwan Xing performed Western blot experiments and conducted data analysis. Haitao Ge and Fujiang Wang critically appraised the paper and gave final suggestions. All authors contributed to the final approval of the manuscript.
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This study was approved by the Animal Ethics Committee of Suzhong Pharmaceutical Group Co., Ltd. (Approval Code: SZSW-2023082401). All methods are reported in accordance with ARRIVE guidelines.
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Li, D., Ge, H., Zhang, Y. et al. Integrated metabolomics and 16S rRNA sequencing reveal the mechanism of total flavones of Abelmoschus manihot (L.) Medic against liver fibrosis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38192-5
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DOI: https://doi.org/10.1038/s41598-026-38192-5
