Jayakumar Thanasekaran, Lin Kao-Chang, Chang Chao-Chien, Hsia Chih-Wei, Manubolu Manjunath, Huang Wei-Chieh, Sheu Joen-Rong, Hsia Chih-Hsuan
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Chi Mei Medical Center, Department of Neurology, Tainan 710, Taiwan.
Int J Mol Sci. 2021 Dec 22;23(1):92. doi: 10.3390/ijms23010092.
Studies have discovered that different extracts of and its phytochemicals show a variety of biological activities associated with inflammation. Although rutaecarpine, an alkaloid isolated from the unripe fruit of , has been exposed to have anti-inflammatory properties, the mechanism of action has not been well studied. Thus, this study investigated the molecular mechanisms of rutaecarpine (RUT) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. RUT reserved the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL)-1β in the LPS-induced macrophages. RUT showed an inhibitory effect on the mitogen-activated protein kinases (MAPKs), and it also inhibited nuclear transcription factor kappa-B (NF-κB) by hindering IκBα and NF-κB p65 phosphorylation and p65 nuclear translocation. The phospho-PI3K and Akt was concentration-dependently suppressed by RUT. However, RUT not only suggestively reduced the migratory ability of macrophages and their numbers induced by LPS but also inhibited the phospho-Src, and FAK. Taken together, these results indicate that RUT participates a vital role in the inhibition of LPS-induced inflammatory processes in RAW 264.7 macrophages and that the mechanisms involve PI3K/Akt and MAPK-mediated downregulation of NF-κB signaling pathways. Notably, reducing the migration and number of cells induced by LPS via inhibiting of Src/FAK pathway was also included to the anti-inflammatory mechanism of RUT. Therefore, RUT may have potential benefits as a therapeutic agent against chronic inflammatory diseases.
研究发现，[植物名称]及其植物化学物质的不同提取物具有多种与炎症相关的生物活性。尽管从[植物名称]未成熟果实中分离出的生物碱吴茱萸次碱已被证实具有抗炎特性，但其作用机制尚未得到充分研究。因此，本研究调查了吴茱萸次碱（RUT）在脂多糖（LPS）诱导的RAW 264.7巨噬细胞中的分子机制。RUT抑制了LPS诱导的巨噬细胞中一氧化氮（NO）的产生以及诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、肿瘤坏死因子（TNF-α）和白细胞介素（IL）-1β的表达。RUT对丝裂原活化蛋白激酶（MAPK）具有抑制作用，并且通过阻碍IκBα和NF-κB p65的磷酸化以及p65的核转位来抑制核转录因子κB（NF-κB）。RUT浓度依赖性地抑制磷酸化磷脂酰肌醇-3激酶（PI3K）和蛋白激酶B（Akt）。然而，RUT不仅显著降低了LPS诱导的巨噬细胞的迁移能力及其数量，还抑制了磷酸化的Src和黏着斑激酶（FAK）。综上所述，这些结果表明RUT在抑制RAW 264.7巨噬细胞中LPS诱导的炎症过程中发挥着重要作用，其机制涉及PI3K/Akt和MAPK介导的NF-κB信号通路的下调。值得注意的是，通过抑制Src/FAK途径减少LPS诱导的细胞迁移和数量也包含在RUT的抗炎机制中。因此，RUT作为一种治疗慢性炎症性疾病的药物可能具有潜在益处。
