Curcumin exerts anti-inflammatory, antioxidant and anti-ferroptotic effects through the Nrf2/HO-1 pathway to protect cardiomyocytes against sepsis

This study explores the therapeutic effect of curcumin on H9c2 rat cardiac myoblasts in vitro sepsis model and its potential mechanisms. At first, Cell viability was measured using Cell Counting Kit 8 (CCK-8) and Cell-Light 5-ethynyl-2-deoxyuridine (EdU) staining, and inflammatory factors tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and Fe2+ were calculated by ELISA and kits. Western blotting was used to quantitatively analyze nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long-chain family (ACSL4) expression differences. Knocking down Nrf2 to study whether curcumin acts through the Nrf2/HO-1 pathway. The results show that curcumin significantly improved cell viability in lipopolysaccharide (LPS)-induced H9c2 cells (p < 0.01). Curcumin also significantly reduced inflammatory factor levels in LPS-induced cardiomyocytes (p < 0.001). Curcumin down-regulated ROS and MDA levels (p < 0.001), and up-regulated SOD and GSH levels (p < 0.001). A decrease in both Fe2+ content and protein expression of ACSL4 (p < 0.001), and increased protein expression of glutathione peroxidase 4 (GPX4) (p < 0.001) were observed with curcumin. By knocking down Nrf2 curcumin’s therapeutic effect against LPS was eliminated. So curcumin can inhibit LPS-induced oxidative stress, inflammation and ferroptosis in cardiomyocytes by regulating Nrf-2/HO-1 signaling.

Cardiomyocytes; Curcumin; Sepsis; Nrf2/HO-1; Ferroptosis; Oxidative stress; Inflammation

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