Inhibition of thioredoxin-interacting protein may enhance the therapeutic effect of dehydrocostus lactone in cardiomyocytes under doxorubicin stimulation via the inhibition of the inflammatory response

Heart failure (HF) is the leading cause of death around the world, the mortality caused by HF is growing rapidly, and has become a great threaten to both public health and economic growth. Dehydrocostus lactone (DHE) is the active constituent of Saussurea lappa and is widely used in traditional Chinese medicine for its multiple biological functions, including anti-inflammatory, antioxidant and anti-cancer. To the best of our knowledge, DHE's effect on HF has not been clarified. Thioredoxin-interacting protein (TXNIP) regulates the process of oxidative stress and inflammation and leads to an increase in oxidative stress via oxidization of thioredoxin, TXNIP promotes the activation of the immune response by its binding with the NOD-like receptor protein 3 inflammasome. An MTT assay revealed that the overexpression or inhibition of TXNIP markedly decreased or significantly increased the proliferation of H9c2 cells, respectively. Through reverse transcription-quantitative PCR (RT-qPCR) and western blotting, it was determined that the expression of proinflammatory cytokines was significantly decreased with the increased expression of anti-inflammatory cytokines in a TXNIP knockout model. Further study utilizing RT-qPCR and western blotting demonstrated that these effects may be mediated by the nuclear factor erythroid 2-related factor 2/heme oxygenase-1/NF-κB signaling pathway. In conclusion, TXNIP inhibition may promote the therapeutic effect of DHE on oxidative stress-induced damage.