2. Academic Validation
  3. Harnessing FDA-approved dipyridamole to inhibit NLRP3 inflammasome and improve outcomes of acute lung injury in sepsis

Harnessing FDA-approved dipyridamole to inhibit NLRP3 inflammasome and improve outcomes of acute lung injury in sepsis

  • Toxicol Appl Pharmacol. 2025 Jul:500:117383. doi: 10.1016/j.taap.2025.117383.
Xiuhui Chen 1,  Yutong Zheng 1,  Xiaofeng Zhang 1,  Anran Zheng 2,  Junjun Huang 2,  Guoliang Deng 1,  Xuna Wu 1,  Yuying Peng 3,  Xiaoling Zhang 4,  Renshan Chen 5,  Qing Xiao 6,  Weijun Ye 7
Affiliations

Affiliations

  • 1 Department of Pharmacy & the Eighth People's Hospital of Dongguan, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan 523000, China; Key Laboratory of Precision Pharmacy and Pharmaceutical Basic Research, Dongguan Institute of Pediatrics, Dongguan 523000, China.
  • 2 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511436, China.
  • 3 Department of Pharmacy & the Eighth People's Hospital of Dongguan, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan 523000, China.
  • 4 Maternal and Children Hospital of Guangdong Province, Guangzhou 511436, China.
  • 5 Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou 511436, China. Electronic address: 21181010228@stu.suse.edu.cn.
  • 6 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: 2012990009@gzhmu.edu.cn.
  • 7 Department of Pharmacy & the Eighth People's Hospital of Dongguan, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan 523000, China; Key Laboratory of Precision Pharmacy and Pharmaceutical Basic Research, Dongguan Institute of Pediatrics, Dongguan 523000, China. Electronic address: yeweijun@ba-hospital.com.
PMID: 40360054 DOI: 10.1016/j.taap.2025.117383
Abstract

Aberrant activation of the NLRP3 inflammasome is critically involved in sepsis-induced acute lung injury (ALI), with inhibition of this pathway emerging as a promising therapeutic approach. This study identifies Dipyridamole, an FDA-approved drug, as a novel inhibitor of the NLRP3 inflammasome. Mechanistically, Dipyridamole suppresses mitochondrial ROS release and directly interacts with NEK7, thereby preventing its association with NLRP3 and impeding inflammasome complex assembly. In an LPS-induced sepsis model, Dipyridamole significantly ameliorated ALI, reduced inflammatory responses, and improved survival rates in model mice. Additionally, Dipyridamole effectively inhibited NLRP3 inflammasome activation in lung tissue. These findings position Dipyridamole as a potent NLRP3 inflammasome inhibitor with substantial therapeutic potential for managing sepsis-induced ALI.

Keywords

Acute lung injury; Dipyridamole; NEK7; NLRP3 inflammasome; ROS; Sepsis.

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