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Metabolomics Combined with Network Pharmacology Uncovers Effective Targets of Tao-Hong-Si-Wu Decoction for Its Protection from Sepsis-Associated Acute Lung Injury

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Abstract

Sepsis-induced acute lung injury (ALI) is a leading cause of death among septic complications. Tao-Hong-Si-Wu decoction (TSD), a classical recipe from traditional Chinese medicine used for treating ischemic stroke, has been recently reported to alleviate inflammation and inflammation-stimulated injuries related to the pathology of ALI. Here, we first observed the therapeutic effect of TSD on sepsis-induced ALI. Based on integrated metabolomics and network pharmacology analysis (NPA) techniques, we aim to understand the mechanism of TSD alleviating ALI. TSD’s effects were observed in rats modeled by cecal ligation and puncture (CLP) and rat macrophages stimulated by lipopolysaccharide (LPS). Metabolomics analyses were applied to determine the ingredients in the medicine and key metabolites correlated to the NPA for the prediction of TSD targets. Gene and protein expressions of the key predicted targets were evaluated in the lung tissue and macrophages of septic model rat by quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays, respectively. TSD improved survival rate and protected against lung injury in CLP rats. Eleven endogenous metabolites were related to TSD’s actions. TSD significantly suppressed IL-6 and TNF-α secretions and their gene expressions both in the lung tissue of the model rats and in LPS-stimulated macrophages. TSD also restored decreased lung protein expression of VEGFA in septic model rats. Targeted proteins and their affecting metabolites were finally validated in an external test set of rats. This study shows that metabolomics coupled with NPA is a promising approach to explore potential targets of medicine with complex compositions.

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Acknowledgements

The authors appreciate the constructive advice on the study design from Prof. Jinfang Ge and Prof. Rong Li. We also thank Mr. Lan Zhang and Mr. Junlong Li for their help with animal experiences.

Funding

The study was supported by the National Natural Science Foundation of China (81873986), Anhui Natural Science Foundation (2008085QH364), the funding of Anhui Medical University (2020xkjT019, 2021lcxk026), and Scientific Research Platform Improvement Project of Anhui Medical University (2022xkjT045).

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  1. Jinzhi He, Longfei Wang and Yang Wang contributed equally to the manuscript.

Authors and Affiliations

  1. Anhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs School of Pharmacy, Anhui Medical University, Hefei, 230032, China

    Jinzhi He, Longfei Wang, Zeng Li, Feihu Chen & Zhicheng Liu

  2. Shanxi Key Laboratory of Big Data for Clinical Decision Research, School of Management, Shanxi Medical University, Taiyuan, 030000, China

    Yang Wang

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  1. Jinzhi He
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Contributions

JH: conceptualization, writing—original draft, formal analysis, investigation; LW: data curation, validation, methodology; writing—original draft; YW: methodology, investigation, validation; ZL: conceptualization, project administration; FC: validation, project administration; ZL: conceptualization, data curation, writing—original draft, validation, project administration. All the authors contributed to the review and editing.

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Correspondence to Zeng Li, Feihu Chen or Zhicheng Liu.

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He, J., Wang, L., Wang, Y. et al. Metabolomics Combined with Network Pharmacology Uncovers Effective Targets of Tao-Hong-Si-Wu Decoction for Its Protection from Sepsis-Associated Acute Lung Injury. J. Anal. Test. 7, 172–186 (2023). https://doi.org/10.1007/s41664-023-00248-0

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