ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1500157
Shenfu injection promotes self-renewal of intestinal stem cells in sepsis-induced intestinal injury via inducing ATF4 expression
Provisionally accepted
- 1Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Beijing, China
- 2Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, China
- 3Jinan City People’s Hospital, Jinan, Shandong Province, China
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Shenfu injection (SFI) is widely used in clinical severe conditions including sepsis due to its pharmacological effects of invigorating Qi and reviving Yang for resuscitation. SFI is known to alleviate sepsis-related intestinal injury. However, the underlying mechanism remains exclusive. This study aimed to investigate the regulatory role of SFI in the self-renewal of intestinal stem cells as well as gut microbiota during sepsis. Compared to the control mice, sepsis induced severe mucosal damage in the intestine, including the decrease of the villus length and the number of crypts, which was significantly inhibited by SFI administration. Plasma levels of D-lactate and intestinal-type fatty acid-binding protein (I-FABP) in septic patients with intestinal dysfunction were significantly reduced following SFI administration. In addition, SFI significantly reduced the levels of pro-inflammatory cytokines Interleukin 1β (IL-1β), Interleukin 6 (IL-6) , and tumor necrosis factor-⍺ (TNF-⍺) in septic mice. Cell proliferation and migration in the intestine were significantly increased in the intestine of septic mice upon SFI treatment. Mechanically, SFI facilitated the expression of activating transcription factor 4 (ATF4) to promote the transcription of SRY-Box Transcription Factor 9 (Sox9), thereby activating the stemness and proliferation of crypt stem cells. Moreover, the gut microbiota composition in septic mice was modulated by SFI administration. In particular, high dose of SFI (HSF) treatment was found to decrease the proportion of harmful bacteria including Proteobacteria and Escherichia-Shigella, while increase the abundance of beneficial bacteria such as Alloprevotella and Butyricimonas in septic mice. Our findings revealed that SFI protects against sepsis-induced intestinal injury via promoting the self-renewal of crypt stem cells and regulating the gut microbiota composition, providing strong evidence for the potential of SFI in treating sepsis-related intestinal dysfunction.
Keywords: Shenfu injection, Sepsis, Intestinal dysfunction, crypt stem cell, Gut Microbiota
Received: 08 Oct 2024; Accepted: 15 Jul 2025.
Copyright: © 2025 Deng, Lu, Li, Gao, Meng, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mei Meng, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China
You Li, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China
Fengyong Yang, Jinan City People’s Hospital, Jinan, Shandong Province, China
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