Zerumin A attenuates the inflammatory responses in LPS‐stimulated H9c2 cardiomyoblasts

Abstract Zerumin A (ZA) is one of the potential components of Curcuma amada rhizomes, and it has been shown to possess a variety of pharmacological activities. This study deals with the beneficial activity of ZA in lipopolysaccharide (LPS)‐stimulated inflammation in H9c2 cardiomyoblasts. Herein, H9c2 cells were preincubated with ZA for 1 h and stimulated with LPS for 24 h. The cells were analyzed for the expression of various pro‐inflammatory mediators and signaling molecules. Results showed that the cell viability was significantly improved and reactive oxygen species production was alleviated remarkably with ZA pretreatment. We also found that ZA pretreatment significantly suppressed the upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2) protein levels, and nitric oxide (NO) release in LPS‐stimulated cells. In addition, ZA significantly ameliorated LPS‐elicited overexpression of pro‐inflammatory chemokines and cytokines such as monocyte chemoattractant protein‐1 (MCP‐1), tumor necrosis factor α (TNF‐ α), interferon‐γ (IFN‐γ), and interleukin‐1 (IL‐1) in H9c2 cells, and it upregulated the synthesis of the anti‐inflammatory cytokine interleukin‐10 (IL‐10). Moreover, pretreatment with ZA and the mitogen‐activated protein kinases (MAPK) pathway inhibitors also reduced the phosphorylation of extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinases (JNK), and p38. ZA significantly inhibited I k B‐a phosphorylation and nuclear factor (NF)‐ k B p65 subunit translocation into nuclei. Overall data demonstrated that ZA protects cardiomyocytes against LPS injury by inhibiting NF‐ k B p65 activation via the MAPK signaling pathway in vitro. These findings suggest that ZA may be a promising agent for a detailed study for the prevention or treatment of myocardial dysfunction in sepsis.