Phytomedicine. 2025 Mar 26;142:156698. doi: 10.1016/j.phymed.2025.156698. Online ahead of print.
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.
PMID:40397999 | DOI:10.1016/j.phymed.2025.156698
