Kumagai Momochika, Watanabe Akio, Yoshida Izumi, Mishima Takashi, Nakamura Munetomo, Nishikawa Keisuke, Morimoto Yoshiki
Japan Food Research Laboratories, Saito Laboratory.
Department of Chemistry, Graduate School of Science, Osaka City University.
Biol Pharm Bull. 2018;41(1):132-137. doi: 10.1248/bpb.b17-00607.
Anti-inflammatory activity of aculeatin and toddaculin, which are coumarins with a similar structure isolated from Toddalia asiatica (L.) LAM., was evaluated using lipopolysaccharide (LPS)-stimulated RAW264 mouse macrophage cells. Both aculeatin and toddaculin significantly inhibited mRNA expression of inflammatory mediators and nitric oxide production. Furthermore, Toddaculin suppressed LPS-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 and inhibited LPS-induced activation of nuclear factor-kappaB (NF-κB). However, aculeatin did not exhibit such effects, suggesting that aculeatin and toddaculin suppress LPS-induced inflammation of RAW264 cells via different mechanisms. The cellular uptake of these compounds was also evaluated. Toddaculin was detected in RAW264 cells after 4 and 24 h. However, aculeatin levels were not observed in RAW264 cells at all incubation intervals. These results indicate that de-epoxidation of a prenyl group can increase hydrophobicity of molecule and is thought to accelerate cellular uptake and/or interactions with the phospholipid bilayers of cell membranes.
从飞龙掌血（Toddalia asiatica (L.) LAM.）中分离得到的结构相似的香豆素类化合物刺桐素和飞龙掌血素的抗炎活性，通过脂多糖（LPS）刺激的RAW264小鼠巨噬细胞进行评估。刺桐素和飞龙掌血素均显著抑制炎症介质的mRNA表达和一氧化氮的产生。此外，飞龙掌血素抑制LPS诱导的p38和细胞外信号调节激酶（ERK）1/2的磷酸化，并抑制LPS诱导的核因子-κB（NF-κB）的激活。然而，刺桐素并未表现出此类作用，这表明刺桐素和飞龙掌血素通过不同机制抑制LPS诱导的RAW264细胞炎症。还评估了这些化合物的细胞摄取情况。在4小时和24小时后，RAW264细胞中检测到飞龙掌血素。然而，在所有孵育时间间隔内，RAW264细胞中均未观察到刺桐素水平。这些结果表明，异戊烯基的去环氧化可增加分子的疏水性，并被认为可加速细胞摄取和/或与细胞膜磷脂双层的相互作用。
