2. Academic Validation
  3. Ophiopogonin C protects against acute lung injury by fatal sepsis through pyroptosis macrophage

Ophiopogonin C protects against acute lung injury by fatal sepsis through pyroptosis macrophage

  • Phytomedicine. 2025 Jul:142:156698. doi: 10.1016/j.phymed.2025.156698.
WeiWei Zhang 1,  Hui Yang 2,  Bangzhi Sui 3,  Yingjing Gui 4,  Jianyu Sun 5,  Yinping Shui 6,  Zhichen Pu 7
Affiliations

Affiliations

  • 1 Department of Pharmacy, Second Affiliated Hospital of Wannan Medical College, Kangfu Road 10(#), Wuhu 241001, Anhui, China.
  • 2 Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wuhu, Anhui 241001, China; Central Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China; Tissue bank of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, China.
  • 3 Department of Pediatric Surgery, Yijishan Hospital of Wannan Medical College, Zheshanxilu 2#, Wuhu, Anhui 241001, China.
  • 4 Cardiovascular and Vascular Surgery, Yijishan Hospital of Wannan Medical College, Zheshanxilu 2#, Wuhu, Anhui 241001, China.
  • 5 Department of Plastic Surgery, the First Affiliated Hospital of Wannan Medical College, Wuhu 241000, China. Electronic address: [email protected].
  • 6 Graduate School, Wannan Medical College, ZheshanxiRoad 2, Wuhu 241001, Anhui, China. Electronic address: [email protected].
  • 7 Department of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241000, China. Electronic address: [email protected].
PMID: 40397999 DOI: 10.1016/j.phymed.2025.156698
Abstract

Background: Sepsis is a frequent complication of severe Infection and trauma, and one of the common causes of acute lung injury (ALI). Macrophage Pyroptosis plays an important role in sepsis-induced ALI, takes part in the regulation of the inflammatory response, and affects the damage and repair of lung tissue.

Purpose: This study attempts to reveal the protective mechanism of Ophiopogonin C against fatal sepsis induced ALI.

Methods: Mice were induced by cecum ligation and puncture (CLP), and treated with 5 (Low), 10 (Med) or 20 (High) mg/kg/day of Ophiopogonin C. Meanwhile, Single-cell data was used to analyze the specific cell lines of Sepsis patients. Molecular docking model also used to identify Protein interaction analysis for DEAD-Box Helicase 3 X-linked gene (DDX3X) binding regions on Nucleotide-binding domain (NBD), leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3).

Results: Ophiopogonin C protected against ALI in the sepsis model. Ophiopogonin C reduced inflammation of macrophage in the ALI sepsis model of ALI. Ophiopogonin C reduced Pyroptosis macrophage in sepsis model of ALI. Pyroptosis macrophage is one important link for Ophiopogonin C in the ALI sepsis model. Ophiopogonin C suppressed NLRP3-induced Pyroptosis macrophage in the ALI sepsis model. The up-regulation of DDX3X expression of macrophage in patients with fatal sepsis by Single-cell RNA Sequencing. Ophiopogonin C suppressed DDX3X expression of macrophage in the ALI sepsis model. DDX3X is an important target spot for Ophiopogonin C in sepsis-induced ALI. Ophiopogonin C combined with the DDX3X protein at N-155 (Asn), R-488 (Arg), and d-506 (Asp) in macrophage. Ophiopogonin C reduced the interaction between the interconnection of DDX3X and NLRP3. Ophiopogonin C suppressed the DDX3X/ NLRP3 Signaling Pathway of human PBMCs by LPS+ATP through the inhibition of Pyroptosis.

Conclusion: These findings demonstrated that Ophiopogonin C safeguards against fatal sepsis-induced ALI through suppressing Pyroptosis in macrophages through mitigating the interaction between DDX3X and NLRP3. Moreover, it offers a potential therapeutic target for fatal sepsis by aiming at the interaction between DDX3X and NLRP3 with Ophiopogonin C.

Keywords

Acute lung injury; DDX3X; Fatal sepsis; NLRP3; Ophiopogonin C; Pyroptosis.

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