Kurniati Dian, Hirai Shizuka, Egashira Yukari
Laboratory of Food and Nutrition, Division of Applied Biochemistry, Graduate School of Horticulture, Chiba University, 648, Matsudo, Matsudo-shi, Chiba, 271-8510, Japan.
Department of Food Technology, Faculty of Agricultural Industrial Technology, Universitas Padjadjaran, Sumedang KM. 21, Jatinangor, 40600, West Java, Indonesia.
Heliyon. 2022 Dec 30;9(1):e12743. doi: 10.1016/j.heliyon.2022.e12743. eCollection 2023 Jan.
[] 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. [] MG6 cells were exposed to LPS with or without API treatment for 24-48 h. and 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. [] LPS suppressed expression and enhanced expression. However, API elevated mRNA expression and suppressed 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. [] These results indicate alteration of 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.
[] 黄酮类芹菜素（API）具有广泛的生物学功能，尤其是抗炎作用。吲哚胺2,3-双加氧酶（IDO）和2-氨基-3-羧基粘康酸-6-半醛脱羧酶（ACMSD）是重要的色氨酸代谢酶，在有毒代谢产物喹啉酸的产生中起关键作用。然而，炎症与ACMSD之间的关系仍不清楚。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测了API对重要色氨酸代谢酶的抗炎作用。 [] 将MG6细胞在有或无API处理的情况下暴露于LPS中24至48小时。分析炎症介质的mRNA表达和产生。还检测了丝裂原活化蛋白激酶（MAPK）和核因子-κB（NF-κB）等炎症信号通路的激活情况，以研究API在炎症状态下的作用机制。 [] LPS抑制了[具体基因1]的表达并增强了[具体基因2]的表达。然而，API提高了LPS处理的MG6细胞中[具体基因1]的mRNA表达并抑制了[具体基因2]的mRNA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的表达并促进了色氨酸的降解。API还抑制细胞外信号调节激酶（Erk）和c-Jun氨基末端激酶（JNK）MAPK的激活以及IκBα的降解。 [] 这些结果表明炎症条件下[具体基因]表达的改变。此外，API恢复了色氨酸代谢关键酶的表达，这可能是通过在LPS刺激的小胶质细胞中使Erk, JNK MAPK和NF-κB通路失活来抑制促炎介质的产生来介导的。
