2. Academic Validation
  3. Paeoniflorin suppresses cardiomyocyte pyroptosis and ameliorates diabetic cardiomyopathy by AMPK/Nrf2/NLRP3 pathway

Paeoniflorin suppresses cardiomyocyte pyroptosis and ameliorates diabetic cardiomyopathy by AMPK/Nrf2/NLRP3 pathway

  • Int Immunopharmacol. 2025 Dec 31:171:116122. doi: 10.1016/j.intimp.2025.116122.
Huixiang Zhang 1,  Xue Yang 1,  Yingwanqi Wang 1,  Wei Xiao 1,  Yu Zhao 1,  Fengkai Wu 2,  Hongyu Liu 3,  Shan Ren 1,  Yang Liu 1,  Yan Lin 4,  Jun Wang 5,  Guangwei Li 6
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Qiqihar Medical University, Qiqihar 161006, China; Key Laboratory of Drug Food Homologous Resources and Metabolic Disease Prevention in Heilongjiang Province, Qiqihar Medical University, Qiqihar 161006, China.
  • 2 Department of Pathology, Qiqihar First Hospital, Qiqihar 161005, China.
  • 3 Department of Cardiothoracic Surgery, Qiqihar First Hospital, Qiqihar 161005, China.
  • 4 Department of Pathophysiology, Qiqihar Medical University, Qiqihar 161006, China; Key Laboratory of Drug Food Homologous Resources and Metabolic Disease Prevention in Heilongjiang Province, Qiqihar Medical University, Qiqihar 161006, China. Electronic address: [email protected].
  • 5 Department of Pathophysiology, Qiqihar Medical University, Qiqihar 161006, China; Key Laboratory of Drug Food Homologous Resources and Metabolic Disease Prevention in Heilongjiang Province, Qiqihar Medical University, Qiqihar 161006, China. Electronic address: [email protected].
  • 6 Department of Pathophysiology, Qiqihar Medical University, Qiqihar 161006, China; Key Laboratory of Drug Food Homologous Resources and Metabolic Disease Prevention in Heilongjiang Province, Qiqihar Medical University, Qiqihar 161006, China. Electronic address: [email protected].
PMID: 41477992 DOI: 10.1016/j.intimp.2025.116122
Abstract

Investigating potential pharmaceutical agents for diabetic cardiomyopathy (DCM) represents a crucial avenue in diabetes research. Paeoniflorin (PF), derived from Plants belonging to the Paeonia genus, has demonstrated potential in addressing cardiovascular conditions; however, its precise mechanism is still uncertain. This research employs various techniques, including MTT assay, ELISA, immunofluorescence, siRNA transfection technology, RT-qPCR, Western blot, and echocardiography, to investigate the protective impacts of PF on type I diabetic mice and H9C2 cells under high glucose conditions, emphasizing inflammatory responses and Pyroptosis. Both the animal and cellular results indicated that PF can ameliorate abnormalities of cardiomyocyte surface area and the expressions of Collagen type I, ANP, and BNP, while ameliorating cardiac function. Concurrently, PF downregulated the levels of various proteins, including NLRP3, Caspase-1, C-Caspase-1, GSDMD, GSDMD-N, as well as reducing the levels of interleukin-1 beta (IL-1β), interleukin-18 (IL-18), and Lactate Dehydrogenase (LDH). These results imply that PF may alleviate high glucose-induced myocardial hypertrophy and fibrosis, ameliorate cardiac function, and mitigate cardiomyocyte Pyroptosis and inflammatory responses. The study reveals that the cardioprotective effects of PF anti-inflammation and anti-pyroptosis may be closely associated with the AMPK/Nrf2/NLRP3 pathway. This research elucidates the mechanism of PF in treating DCM by inhibiting Pyroptosis and inflammatory responses, thereby providing new insights for the clinical prevention and treatment of DCM.

Keywords

AMPK; Diabetic cardiomyopathy; NLRP3 inflammasome; Nrf2; Paeoniflorin; Pyroptosis.

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