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

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.