Sepsis is a life-threatening organ dysfunction caused by the dysregulated response of the host to an infection, and treatments are limited. Recently, a novel selenium source, selenium-enriched Cardamine violifolia(SEC...Sepsis is a life-threatening organ dysfunction caused by the dysregulated response of the host to an infection, and treatments are limited. Recently, a novel selenium source, selenium-enriched Cardamine violifolia(SEC) has attracted much attention due to its anti-inflammatory and antioxidant properties, but little is known about its role in the treatment of sepsis. Here, we found that SEC alleviated LPS-induced intestinal damage, as indicated by improved intestinal morphology, and increased disaccharidase activity and tight junction protein expression. Moreover, SEC ameliorated the LPS-induced release of pro-inflammatory cytokines, as indicated by decreased IL-6 level in the plasma and jejunum. Moreover, SEC improved intestinal antioxidant functions by regulating oxidative stress indicators and selenoproteins. In vitro, TNF-α-challenged IPEC-1 cells were examined and showed that selenium-enriched peptides, which are the main functional components extracted from Cardamine violifolia(CSP), increased cell viability, decreased lactate dehydrogenase activity and improved cell barrier function. Mechanistically, SEC ameliorated LPS/TNF-α-induced perturbations in mitochondrial dynamics in the jejunum and IPEC-1 cells. Moreover, CSPmediated cell barrier function is primarily dependent on the mitochondrial fusion protein MFN2 but not MFN1. Taken together,these results indicate that SEC mitigates sepsis-induced intestinal injury, which is associated with modulating mitochondrial fusion.展开更多
基金supported by the National Natural Science Foundation of China (U22A20517, 32272906 and 32102566)the Project of Wuhan Science and Technology Bureau (2022020801010391)。
文摘Sepsis is a life-threatening organ dysfunction caused by the dysregulated response of the host to an infection, and treatments are limited. Recently, a novel selenium source, selenium-enriched Cardamine violifolia(SEC) has attracted much attention due to its anti-inflammatory and antioxidant properties, but little is known about its role in the treatment of sepsis. Here, we found that SEC alleviated LPS-induced intestinal damage, as indicated by improved intestinal morphology, and increased disaccharidase activity and tight junction protein expression. Moreover, SEC ameliorated the LPS-induced release of pro-inflammatory cytokines, as indicated by decreased IL-6 level in the plasma and jejunum. Moreover, SEC improved intestinal antioxidant functions by regulating oxidative stress indicators and selenoproteins. In vitro, TNF-α-challenged IPEC-1 cells were examined and showed that selenium-enriched peptides, which are the main functional components extracted from Cardamine violifolia(CSP), increased cell viability, decreased lactate dehydrogenase activity and improved cell barrier function. Mechanistically, SEC ameliorated LPS/TNF-α-induced perturbations in mitochondrial dynamics in the jejunum and IPEC-1 cells. Moreover, CSPmediated cell barrier function is primarily dependent on the mitochondrial fusion protein MFN2 but not MFN1. Taken together,these results indicate that SEC mitigates sepsis-induced intestinal injury, which is associated with modulating mitochondrial fusion.
