Dihydroartemisinin alleviates mitochondrial damage and improves cardiomyocyte pyroptosis and ferroptosis through Sirt1-mediated PGC-1a

This study assesses the effect of dihydroartemisinin on pyroptosis and ferroptosis. Rat H9C2 cardiomyocytes were intervened with 35 mmol/L high glucose through assigned blank control, dihydro artemisinin, and dihydroartemisinin + Sirt1 groups. Confocal microscopy was used to observe the ROS levels, while proliferation ability was detected by CCK-8 method, and apoptosis was assessed by flow cytometry, and migration ability by Transwell transfer method. Moreover, analysis of pyroptosis-related factors expression and content of lipid peroxide were done usingIP: 03.8laser 109.20 confocal On: Tue, microscopy. 08 A g The 2023 average 05:03:39 fluorescence intensity of dihydro artemisinin group and dihydroartemisinin + SIRT 1 group decreased significantly (P < 0.05), among which Copyright: Ameri an Sc entific Publ shers the dihydroartemisinin + SIRT 1 group had lowest average fluorescence intensity (P < 0.05). SIRT 1 level in Delivered by Ingenta the dihydroartemisinin and dihydroartemisinin + SIRT 1 groups was higher than blank control (P < 0.05), with highest level in the dihydroartemisinin + SIRT 1 group (P < 0.05). Cell proliferation in the dihydroartemisinin and dihydroartemisinin + SIRT 1 group was reduced (P < 0.05), with lowest proliferation in combination group (P < 0.05). Cell migration in the dihydroartemisinin and dihydroartemisinin + SIRT 1 groups was reduced (P < 0.05), with lowest number of migratory cells in the dihydroartemisinin + SIRT 1 group (P < 0.05). Cell apoptosis in the dihydroartemisinin and dihydroartemisinin + SIRT 1 groups was increased (P < 0.05), with lowest apoptosis in the dihydroartemisinin + SIRT 1 group (P < 0.05). There was upregulation of SIRT 1 and PGC-1a mRNA expression in the dihydroartemisinin and dihydroartemisinin + SIRT 1 groups was elevated (P < 0.05). The expression of NLRP3, GSDMD, and Caspase-1 were all decreased (P < 0.05), while that of GPX4 was increased (P < 0.05). Dihydroartemisinin inhibits the function of H9C2 cardiomyocytes, pyroptosis and ferroptosis, playing a positive role in ameliorating Diabetic cardiomyopathy (DCM).