Curcumin synergistically improves mitochondrial dynamics and myocardial cell bioenergy after sepsis through the SIRT1-Drp1/PGC-1α pathway

Abstract

Abstract Septic cardiomyopathy (SCM) is associated with an imbalance in mitochondrial quality and high mortality rates, and an effective treatment has not been developed to date. Curcumin provides antioxidant, anti-inflammatory, cardiovascular, and mitochondrial protection. However, it has not been confirmed to improve cardiac dysfunction in sepsis and reduce abnormal inflammatory responses by improving mitochondrial function. Herein, we explore novel mechanisms by which curcumin improves SCM using an in vivo male C57BL/6 mice sepsis model and in vitro HL-1 cells stimulated with lipopolysaccharide. Curcumin’s effects on sepsis-induced cardiac dysfunction, inflammatory responses, and mitochondrial quality of cardiac cells were observed using qPCR, western blotting, echocardiography, and transmission electron microscopy. Curcumin-activated sirtuin 1 (SIRT1) increased the expression of mitochondrial biogenesis-related genes PGC-1α, TFAM, and Nrf2, reduced dynamin-related protein 1 (Drp1) translocation from the cytoplasm to mitochondria, and restored the mitochondrial morphology and function in cardiac cells, thus protecting heart function after septic shock and alleviating the effects of SCM. SIRT1 knockdown reversed the protective effects of curcumin on mitochondria. Curcumin promotes mitochondrial biogenesis and inhibits mitochondrial fragmentation by activating SIRT1, thereby improving the mitochondrial quality and reducing oxidative stress in cardiomyocytes and sepsis-induced cardiac dysfunction. These findings provide new evidence supporting the use of curcumin to treat SCM.