2. Academic Validation
  3. Shenfu injection targets the PI3K-AKT pathway to regulate autophagy and apoptosis in acute respiratory distress syndrome caused by sepsis

Shenfu injection targets the PI3K-AKT pathway to regulate autophagy and apoptosis in acute respiratory distress syndrome caused by sepsis

  • Phytomedicine. 2024 Jul:129:155627. doi: 10.1016/j.phymed.2024.155627.
Juan Chen 1,  Weichao Ding 2,  Zhe Zhang 3,  Quan Li 4,  Mengmeng Wang 5,  Jing Feng 5,  Wei Zhang 5,  Liping Cao 5,  Xiaohang Ji 5,  Shinan Nie 6,  Zhaorui Sun 7
Affiliations

Affiliations

  • 1 Department of Emergency Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, PR China; Department of Emergency Medicine, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu Province 221000, PR China.
  • 2 Department of Emergency Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, PR China; Department of Emergency Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, PR China.
  • 3 Department of Emergency Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210002, PR China; Department of Medical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, PR China.
  • 4 Department of Emergency Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210002, PR China.
  • 5 Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, PR China.
  • 6 Department of Emergency Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, PR China. Electronic address: [email protected].
  • 7 Department of Emergency Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, PR China. Electronic address: [email protected].
PMID: 38696924 DOI: 10.1016/j.phymed.2024.155627
Abstract

Background: Sepsis is a life-threatening organ dysfunction caused by an exaggerated response to Infection. In the lungs, one of the most susceptible organs, this can manifest as acute respiratory distress syndrome (ARDS). Shenfu (SF) injection is a prominent traditional Chinese medicine used to treat sepsis. However, the exact mechanism of its action has rarely been reported in the literature.

Purpose: In the present study, we detected the protective effect of SF injection on sepsis-induced ARDS and explored its underlying mechanism.

Methods: We investigated the potential targets and regulatory mechanisms of SF injections using a combination of network pharmacology and RNA Sequencing. This study was conducted both in vivo and in vitro using a mouse model of ARDS and lipopolysaccharide (LPS)-stimulated MLE-12 cells, respectively.

Results: The results showed that SF injection could effectively inhibit inflammation, oxidative stress, and Apoptosis to alleviate LPS-induced ARDS. SF inhibited the PI3K-AKT pathway, which controls Autophagy and Apoptosis. Subsequently, MLE-12 cells were treated with 3-methyladenine to assess its effects on Autophagy and Apoptosis. Additional experiments were conducted by adding rapamycin, an mTOR antagonist, or SC79, an Akt Agonist, to investigate the effects of SF injection on Autophagy, Apoptosis, and the PI3K-AKT pathway.

Conclusion: Overall, we found that SF administration could enhance autophagic activity, reduce Apoptosis, suppress inflammatory responses and oxidative stress, and inhibit the PI3K-AKT pathway, thus ameliorating sepsis-induced ARDS.

Keywords

Acute respiratory distress syndrome; Apoptosis; Autophagy; PI3K-AKT pathway; Sepsis; Shenfu injection.

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