Jeju Inside Agency & Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Korea.
Molecules. 2021 Sep 2;26(17):5351. doi: 10.3390/molecules26175351.
Persistent inflammatory reactions promote mucosal damage and cause dysfunction, such as pain, swelling, seizures, and fever. Therefore, in this study, in order to explore the anti-inflammatory effect of 6-methylcoumarin (6-MC) and suggest its availability, macrophages were stimulated with lipopolysaccharide (LPS) to conduct an in vitro experiment. The effects of 6-MC on the production and levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α) and inflammatory mediators (nitric oxide (NO), prostaglandin E (PGE)) in LPS-stimulated RAW 264.7 cells were examined. The results showed that 6-MC reduced the levels of NO and PGE without being cytotoxic. In addition, it was demonstrated that the increase in the expression of pro-inflammatory cytokines caused by LPS stimulation, was decreased in a concentration-dependent manner with 6-MC treatment. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which increased with LPS treatment, were decreased by 6-MC treatment. Mechanistic studies revealed that 6-MC reduced the phosphorylation of the mitogen-activated protein kinase (MAPK) family and IκBα in the MAPK and nuclear factor-kappa B (NF-κB) pathways, respectively. These results suggest that 6-MC is a potential therapeutic agent for inflammatory diseases that inhibits inflammation via the MAPK and NF-κB pathways.
持续的炎症反应会促进黏膜损伤，并导致功能障碍，如疼痛、肿胀、癫痫发作和发热。因此，在这项研究中，为了探索 6-甲基香豆素（6-MC）的抗炎作用，并表明其可用性，用脂多糖（LPS）刺激巨噬细胞进行体外实验。研究了 6-MC 对 LPS 刺激的 RAW 264.7 细胞中促炎细胞因子（白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α）和炎症介质（一氧化氮（NO）、前列腺素 E（PGE））产生和水平的影响。结果表明，6-MC 降低了 NO 和 PGE 的水平而没有细胞毒性。此外，还表明 6-MC 处理可降低 LPS 刺激引起的促炎细胞因子表达的增加，呈浓度依赖性。此外，Western blot 结果表明，LPS 处理增加的诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）蛋白水平，通过 6-MC 处理而降低。机制研究表明，6-MC 分别降低了丝裂原活化蛋白激酶（MAPK）家族和核因子-κB（NF-κB）途径中 MAPK 和 IκBα的磷酸化。这些结果表明，6-MC 通过 MAPK 和 NF-κB 途径抑制炎症，是一种治疗炎症性疾病的潜在治疗剂。
