Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701 ; Department of Radiology, Dongguk University Ilsan Hospital, Ilsan 410-773, Republic of Korea.
Biomol Ther (Seoul). 2014 May;22(3):200-6. doi: 10.4062/biomolther.2014.013.
N-(p-Coumaryol) tryptamine (CT), a phenolic amide, has been reported to exhibit anti-oxidant and anti-inflammatory activities. However, the underlying mechanism by which CT exerts its pharmacological properties has not been clearly demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of CT in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. CT significantly inhibited LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and PGE2, and protein expressions of iNOS and COX-2. In addition, CT significantly suppressed LPS-induced secretion of pro-inflammatory cytokines such as TNF-α and IL-1β. To elucidate the underlying anti-inflammatory mechanism of CT, involvement of MAPK and Akt signaling pathways was examined. CT significantly attenuated LPS-induced activation of JNK/c-Jun, but not ERK and p38, in a concentration-dependent manner. Interestingly, CT appeared to suppress LPS-induced Akt phosphorylation. However, JNK inhibition, but not Akt inhibition, resulted in the suppression of LPS-induced responses, suggesting that JNK/c-Jun signaling pathway significantly contributes to LPS-induced inflammatory responses and that LPS-induced Akt phosphorylation might be a compensatory response to a stress condition. Taken together, the present study clearly demonstrates CT exerts anti-inflammatory activity through the suppression of JNK/c-Jun signaling pathway in LPS-challenged RAW264.7 macrophage cells.
N-(对香豆酰基)色胺（CT）是一种酚酰胺，已被报道具有抗氧化和抗炎活性。然而，CT 发挥其药理学特性的潜在机制尚未得到明确证实。本研究旨在阐明 CT 在脂多糖（LPS）刺激的 RAW264.7 巨噬细胞中抗炎的作用机制。CT 显著抑制 LPS 诱导的促炎介质如一氧化氮（NO）和 PGE2 以及诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的蛋白表达的细胞外分泌。此外，CT 显著抑制 LPS 诱导的促炎细胞因子如 TNF-α和 IL-1β的分泌。为了阐明 CT 的潜在抗炎机制，研究了 MAPK 和 Akt 信号通路的参与。CT 以浓度依赖性方式显著减弱 LPS 诱导的 JNK/c-Jun 的激活，但不影响 ERK 和 p38。有趣的是，CT 似乎抑制了 LPS 诱导的 Akt 磷酸化。然而，JNK 抑制而非 Akt 抑制导致 LPS 诱导的反应被抑制，表明 JNK/c-Jun 信号通路显著参与 LPS 诱导的炎症反应，而 LPS 诱导的 Akt 磷酸化可能是应激条件下的一种代偿反应。综上所述，本研究清楚地表明 CT 通过抑制 LPS 刺激的 RAW264.7 巨噬细胞中 JNK/c-Jun 信号通路发挥抗炎作用。
