Shyni G L, Renjitha J, B Somappa Sasidhar, Raghu K G
Biochemistry and Molecular Mechanism Laboratory, Agro-Processing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, India.
Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, India.
J Biochem Mol Toxicol. 2021 Jun;35(6):1-11. doi: 10.1002/jbt.22777. Epub 2021 Mar 23.
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 IkB-a phosphorylation and nuclear factor (NF)-kB p65 subunit translocation into nuclei. Overall data demonstrated that ZA protects cardiomyocytes against LPS injury by inhibiting NF-kB 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.
姜黄莪术醇（ZA）是莪术根茎的潜在成分之一，已显示具有多种药理活性。本研究探讨了ZA在脂多糖（LPS）刺激的H9c2心肌成纤维细胞炎症中的有益作用。在此，H9c2细胞先用ZA预孵育1小时，然后用LPS刺激24小时。分析细胞中各种促炎介质和信号分子的表达。结果表明，ZA预处理可显著提高细胞活力，并显著减轻活性氧的产生。我们还发现，ZA预处理可显著抑制LPS刺激细胞中诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）蛋白水平的上调以及一氧化氮（NO）的释放。此外，ZA显著改善了LPS诱导的H9c2细胞中促炎趋化因子和细胞因子如单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子α（TNF-α）、干扰素-γ（IFN-γ）和白细胞介素-1（IL-1）的过度表达，并上调了抗炎细胞因子白细胞介素-10（IL-10）的合成。此外，ZA和丝裂原活化蛋白激酶（MAPK）途径抑制剂预处理也降低了细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和p38的磷酸化。ZA显著抑制IkB-α磷酸化和核因子（NF）-κB p65亚基向细胞核的转位。总体数据表明，ZA在体外通过MAPK信号通路抑制NF-κB p65激活，从而保护心肌细胞免受LPS损伤。这些发现表明，ZA可能是一种有前途的药物，可用于详细研究脓毒症中预防或治疗心肌功能障碍。
