Kim Chae-Hyun, Kwon Yong-Jin, Jang Young-Ah
Department of Cosmeceutical Science, Kyungsung University, Busan 48434, Republic of Korea.
Department of Cosmetic Science, Kyungsung University, Busan 48434, Republic of Korea.
Pharmaceutics. 2024 Mar 5;16(3):365. doi: 10.3390/pharmaceutics16030365.
Corticosteroids are commonly used anti-inflammatory agents. However, their prolonged use can lead to side effects. Therefore, the development of natural compounds with minimal side effects is necessary. This study was performed to investigate the anti-inflammatory effects and mechanisms of action of (Siebold & Zucc.) Endl. leaf (COL), bioconverted using () in lipopolysaccharide (LPS)-induced RAW264.7 cells. The COL 70% EtOH extract fermented by (70COLGA) improved the high cytotoxicity of 70% EtOH extracts (70COL). When RAW264.7 cells were pre-treated with 100 and 200 μg/mL of 70COLGA for 2 h and then treated with LPS for 16 h, LPS induced the production of nitric oxide (NO), and the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were significantly inhibited. When RAW264.7 cells were pre-treated with 100 and 200 μg/mL of 70COLGA for 2 h and then treated with LPS for 4 h, the phosphorylation of signal transducers and activators of transcription (STAT) was markedly decreased. In addition, 70COLGA markedly suppressed the production of the inflammatory cytokines interleukin (IL)-1β and IL-6 in LPS-induced RAW264.7 cells. Analysis of pro-inflammatory molecules using cytokine arrays showed that macrophage inflammatory protein (MIP)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and IL-27 expressions were also suppressed by 200 μg/mL of 70COLGA in LPS-induced RAW264.7 cells. These results demonstrate that 70COLGA significantly prevented inflammatory responses by inhibiting the secretion of pro-inflammatory molecules in LPS-induced RAW264.7 cells. When RAW264.7 cells were pre-treated with 100 and 200 μg/mL of 70COLGA for 2 h and then treated with LPS-conditioned medium (LPS-CM) for 30 min, 70COLGA directly inhibited STAT activation. In summary, our findings suggest that 70COLGA has therapeutic potential for the treatment of inflammatory diseases.
皮质类固醇是常用的抗炎药。然而，长期使用它们会导致副作用。因此，开发副作用最小的天然化合物是必要的。本研究旨在探讨经酿酒酵母生物转化的海州常山叶（COL）在脂多糖（LPS）诱导的RAW264.7细胞中的抗炎作用及作用机制。由酿酒酵母发酵的COL 70%乙醇提取物（70COLGA）改善了70%乙醇提取物（70COL）的高细胞毒性。当RAW264.7细胞用100和200μg/mL的70COLGA预处理2小时，然后用LPS处理16小时时，LPS诱导一氧化氮（NO）的产生，而诱导型一氧化氮合酶（iNOS）和环氧化酶2（COX-2）的表达受到显著抑制。当RAW264.7细胞用100和200μg/mL的70COLGA预处理2小时，然后用LPS处理4小时时，信号转导和转录激活因子（STAT）的磷酸化明显降低。此外，70COLGA显著抑制LPS诱导的RAW264.7细胞中炎性细胞因子白细胞介素（IL）-1β和IL-6的产生。使用细胞因子阵列分析促炎分子表明，在LPS诱导的RAW264.7细胞中，200μg/mL的70COLGA也抑制了巨噬细胞炎性蛋白（MIP）-2、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、粒细胞集落刺激因子（G-CSF）和IL-27的表达。这些结果表明，70COLGA通过抑制LPS诱导的RAW264.7细胞中促炎分子的分泌，显著预防了炎症反应。当RAW264.7细胞用100和200μg/mL的70COLGA预处理2小时，然后用LPS条件培养基（LPS-CM）处理30分钟时，70COLGA直接抑制STAT激活。总之，我们的研究结果表明，70COLGA在治疗炎症性疾病方面具有治疗潜力。
