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Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.

Methods

A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.

Results

FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).

Conclusion

FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

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Authors and Affiliations

  1. Department of Critical Care Medicine, Changzhou Hospital of Traditional of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Changzhou, Jiangsu Province, 213000, China

    Yi Wang

  2. Department of Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210029, China

    Ming-qi Chen, Lin-feng Dai, Hai-dong Zhang & Xing Wang

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  1. Yi Wang
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  2. Ming-qi Chen
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  3. Lin-feng Dai
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  4. Hai-dong Zhang
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  5. Xing Wang
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Contributions

Wang Y, Chen MQ, Wang X, and Dai LF designed the study. Wang Y, Chen MQ and Dai LF conducted the experiment and collated the data, carried out data analyses and produced the initial draft of the manuscript. Zhang HD and Wang X drafted the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Xing Wang.

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Wang, Y., Chen, Mq., Dai, Lf. et al. Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway. Chin. J. Integr. Med. 30, 230–242 (2024). https://doi.org/10.1007/s11655-023-3601-8

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  • DOI: https://doi.org/10.1007/s11655-023-3601-8

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