Swietenine alleviated cardiomyocyte inflammation in diabetic cardiomyopathy by regulating NAMPT/SIRT1.

Inflammation plays a critical role in the pathogenesis of diabetic cardiomyopathy (DCM), with NLRP3 inflammasome activation emerging as a central pathological driver. Swietenine, a limonoid compound derived from Swietenia macrophylla, exhibits multiple pharmacological properties, including anti-inflammatory, hypoglycemic, and antihypertensive effects. This study aimed to investigate the therapeutic potential of swietenine in DCM and elucidate its underlying molecular mechanisms. Using db/db murine models and high-glucose-stimulated H9C2 cardiomyocytes, we demonstrated that swietenine administration improved cardiac function in diabetic mice, attenuated myocardial hypertrophy and fibrosis, and suppressed NLRP3 inflammasome activation. Mechanistically, swietenine treatment significantly downregulated cleaved Caspase-1 p20, pro-IL-18, pro-IL-1β, mature IL-18 and IL-1β, alongside upregulated NAMPT and SIRT1 protein levels. In vitro siRNA-mediated NAMPT knockdown abolished swietenines anti-inflammatory effects, while SIRT1 activation with SRT1720 restored its NLRP3 inhibitory capacity. Collectively, these findings indicate that swietenine ameliorates DCM via the NAMPT/SIRT1 pathway-mediated suppression of NLRP3 inflammasome activation, highlighting its potential as a therapeutic agent for DCM.