PDF(Pubmed)
Abstract：
[Aims] Flavonoid apigenin (API) has a wide range of biological functions, particularly anti-inflammation. Indoleamine 2,3-dioxygenase (IDO) and 2-Amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD) are important tryptophan metabolic enzymes that play pivotal roles in the production of toxic metabolite quinolinic acid. However, the relationship between inflammation and ACMSD remains unclear. The present study investigated the relationship between inflammation and tryptophan metabolic key enzymes. Similarly, the anti-inflammatory effect of API on important tryptophan metabolic enzymes was examined in lipopolysaccharide (LPS)-treated microglial cells. [Main methods] MG6 cells were exposed to LPS with or without API treatment for 24-48 h. IDO and ACMSD mRNA expression and production of inflammatory mediators were analyzed. Activation of inflammatory signaling pathways, such as mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB), was also examined to study the mechanism of API in the inflammatory state. [Key findings] LPS suppressed ACMSD expression and enhanced IDO expression. However, API elevated ACMSD mRNA expression and suppressed IDO mRNA expression in LPS-treated MG6 cells. Furthermore, API suppressed interleukin-6 and nitric oxide production, whereas overproduction of inflammatory mediators enhanced IDO expression and assisted tryptophan degradation. API also inhibited activation of extracellular signal-regulated kinase (Erk) and jun N-terminal kinase (JNK) MAPK, and degradation of IκBα. [Significance] These results indicate alteration of ACMSD expression under inflammatory conditions. Moreover, API recovers expression of tryptophan metabolic key enzymes, which may be mediated by inhibition of proinflammatory mediator production via inactivation of Erk, JNK MAPK, and NF-κB pathways in LPS-stimulated microglial cells.
摘要：
[目的]黄酮芹菜素(API)具有广泛的生物学功能,特别是抗炎。吲哚胺2,3-双加氧酶（IDO）和2-氨基-3-羧基羧酸-6-半醛脱羧酶（ACMSD）是重要的色氨酸代谢酶，在有毒代谢物喹啉酸的产生中起关键作用。然而,炎症与ACMSD之间的关系尚不清楚.本研究调查了炎症与色氨酸代谢关键酶之间的关系。同样，在脂多糖（LPS）处理的小胶质细胞中检查了API对重要色氨酸代谢酶的抗炎作用。[主要方法]将MG6细胞暴露于有或没有API处理的LPS中24-48h。分析IDO和ACMSDmRNA的表达和炎症介质的产生。炎症信号通路的激活，如丝裂原活化蛋白激酶（MAPK）和核因子-κB（NF-κB），还检查了API在炎症状态下的机制。[重要发现]LPS抑制ACMSD表达,增强IDO表达。然而,API在LPS处理的MG6细胞中升高ACMSDmRNA表达并抑制IDOmRNA表达。此外，API抑制白细胞介素-6和一氧化氮的产生，而炎症介质的过量产生增强了IDO表达并辅助色氨酸降解。API还抑制细胞外信号调节激酶（Erk）和junN末端激酶（JNK）MAPK的激活，和IκBα的降解。[意义]这些结果表明在炎症条件下ACMSD表达的改变。此外，原料药可恢复色氨酸代谢关键酶的表达，这可能是通过Erk失活抑制促炎介质的产生而介导的，JNKMAPK,和LPS刺激的小胶质细胞中的NF-κB通路。
