Berberine blocks inflammasome activation and alleviates diabetic cardiomyopathy via the miR­18a­3p/Gsdmd pathway.

Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural compound extracted from a Chinese herb, with a clinically reported anti­DCM effect; however, its molecular mechanisms have not yet been fully elucidated. The present study indicated that BBR markedly alleviated DCM by inhibiting IL­1ß secretion and the expression of gasdermin D (Gsdmd) at the post­transcriptional level. Considering the importance of microRNAs (miRNAs/miRs) in the regulation of the post­transcriptional process of specific genes, the ability of BBR to upregulate the expression levels of miR­18a­3p by activating its promoter (­1,000/­500) was examined. Notably, miR­18a­3p targeted Gsdmd and abated pyroptosis in high glucose­treated H9C2 cells. Moreover, miR­18a­3p overexpression inhibited Gsdmd expression and improved biomarkers of cardiac function in a rat model of DCM. On the whole, the findings of the present study indicate that BBR alleviates DCM by inhibiting miR­18a­3p­mediated Gsdmd activation; thus, BBR may be considered a potential therapeutic agent for the treatment of DCM.