Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan.
Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8572, Japan.
Int J Mol Sci. 2023 Apr 3;24(7):6666. doi: 10.3390/ijms24076666.
The present study aimed to evaluate the effects of ethanol extract (BTEE) on lipopolysaccharide (LPS)-induced inflammation in RAW264 cells. BTEE significantly attenuated LPS-induced nitric oxide production and inflammatory cytokines release, including , , and . On the other hand, several anti-inflammatory mediators, such as and , were increased in BTEE-treated cells. Further, we performed an untargeted whole-genome microarray analysis to explore the anti-inflammatory molecular mechanism of BTEE. Enrichment analysis showed BTEE significantly downregulated 'response to stimulus', 'locomotion', and 'immune system response' and upregulated 'cell cycle' gene ontologies in both 6- and 17-h post-LPS stimulation conditions. Pathway analysis revealed BTEE could downregulate the expressions of chemokines of the CC and CXC subfamily, and cytokines of the TNF family, TGFβ family, IL1-like, and class I helical. PPI analysis showed AXL receptor tyrosine kinase (), a receptor tyrosine kinase from the TAM family, and its upstream transcription factors were downregulated in both conditions. Node neighborhood analysis showed several coexpressed genes were also downregulated. Further, kinase enrichment and chemical perturbation analyses supported inhibition in BTEE-treated conditions. Altogether, these findings suggest anti-inflammatory effects of BTEE that are mediated via the suppression of pro-inflammatory cytokines and predict its potential as an inhibitor.
本研究旨在评估乙醇提取物（BTEE）对脂多糖（LPS）诱导的 RAW264 细胞炎症的影响。BTEE 显著减弱了 LPS 诱导的一氧化氮产生和炎症细胞因子释放，包括 TNF-α、IL-1β 和 IL-6。另一方面，BTEE 处理的细胞中几种抗炎介质，如 iNOS 和 HO-1，增加。此外，我们进行了非靶向全基因组微阵列分析，以探讨 BTEE 的抗炎分子机制。富集分析显示，BTEE 在 LPS 刺激后 6 和 17 小时的条件下，显著下调了“对刺激的反应”、“运动”和“免疫系统反应”，并上调了“细胞周期”基因本体论。通路分析显示，BTEE 可下调趋化因子 CC 和 CXC 亚家族以及细胞因子 TNF 家族、TGFβ 家族、IL1 样和 I 类螺旋的表达。PPI 分析显示，AXL 受体酪氨酸激酶（），TAM 家族的受体酪氨酸激酶，及其上游转录因子在两种情况下均下调。节点邻域分析显示，几个共同表达的基因也下调。此外，激酶富集和化学扰动分析支持 BTEE 处理条件下的抑制作用。总之，这些发现表明 BTEE 通过抑制促炎细胞因子发挥抗炎作用，并预测其作为一种有效的 抑制剂的潜力。
