Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Am J Chin Med. 2014;42(4):869-89. doi: 10.1142/S0192415X14500554.
Inflammation is a serious health issue worldwide that induces many diseases, such as inflammatory bowel disease (IBD), sepsis, acute pancreatitis and lung injury. Thus, there is a great deal of interest in new methods of limiting inflammation. In this study, we investigated the leaves of Nelumbo nucifera Gaertn, an aquatic perennial plant cultivated in eastern Asia and India, in anti-inflammatory pharmacological effects in the murine macrophage cell line RAW264.7. Results showed that lipopolysaccharide (LPS) increased the protein expression of inducible nitric oxide synthase (iNOS) and COX-2, as well as the mRNA expression and level of IL-6 and TNF-α, while NNE significantly reduced these effects of LPS. LPS also induced phospho-JNK protein expression. The JNK-specific inhibitor SP600125 decreased the proteins expression of phospho-JNK, iNOS, COX-2, and the mRNAs expression and levels of IL-6 and TNF-α. Further, NNE reduced the protein expression of phospho-JNK. LPS was also found to promote the translocation of NF-κB from the cytosol to the nucleus and to decrease the expression of cytosolic IκB. NNE and SP600125 treatment recovered the LPS-induced expression of NF-κB and IκB. While phospho-ERK and phospho-p38 induced by LPS, could not be reversed by NNE. To further investigate the major components of NNE in anti-inflammatory effects, we determined the quercetin and catechin in inflammatory signals. Results showed that quercetin and catechin significantly decreased the proteins expression of iNOS, COX-2 and phospho-JNK. Besides, the mRNAs and levels of IL-6 and TNF-α also decreased by quercetin and catechin treatment in LPS-induced RAW264.7 cells. These results showed that NNE and its major components quercetin and catechin exhibit anti-inflammatory activities by inhibiting the JNK- and NF-κB-regulated pathways and could therefore be an useful anti-inflammatory agent.
炎症是全球范围内的一个严重健康问题，可引发多种疾病，如炎症性肠病（IBD）、败血症、急性胰腺炎和肺损伤。因此，人们对限制炎症的新方法产生了浓厚的兴趣。在这项研究中，我们研究了在亚洲东部和印度种植的水生多年生植物荷花（Nelumbo nucifera Gaertn）的叶子在抗鼠巨噬细胞系 RAW264.7 中的抗炎药理作用。结果表明，脂多糖（LPS）增加了诱导型一氧化氮合酶（iNOS）和 COX-2 的蛋白表达，以及 IL-6 和 TNF-α 的 mRNA 表达和水平，而 NNE 显著降低了 LPS 的这些作用。LPS 还诱导了磷酸化 JNK 蛋白的表达。JNK 特异性抑制剂 SP600125 降低了磷酸化 JNK、iNOS、COX-2 的蛋白表达以及 IL-6 和 TNF-α 的 mRNAs 表达和水平。此外，NNE 降低了磷酸化 JNK 的蛋白表达。LPS 还促进 NF-κB 从细胞质向核内易位，并降低细胞质 IκB 的表达。NNE 和 SP600125 处理恢复了 LPS 诱导的 NF-κB 和 IκB 的表达。而 LPS 诱导的磷酸化 ERK 和磷酸化 p38 则不能被 NNE 逆转。为了进一步研究 NNE 在抗炎作用中的主要成分，我们测定了炎症信号中 quercetin 和 catechin 的含量。结果表明，quercetin 和 catechin 显著降低了 iNOS、COX-2 和磷酸化 JNK 的蛋白表达。此外，quercetin 和 catechin 处理还降低了 LPS 诱导的 RAW264.7 细胞中 IL-6 和 TNF-α 的 mRNAs 和水平。这些结果表明，NNE 及其主要成分 quercetin 和 catechin 通过抑制 JNK 和 NF-κB 调节途径发挥抗炎作用，因此可能是一种有用的抗炎剂。
