State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Mar Drugs. 2021 Jul 28;19(8):429. doi: 10.3390/md19080429.
RKC-B1 is a novel fermentation product obtained from the marine micromonospora FIM02-523A. Thus far, there have been few reports about the pharmacological activity of RKC-B1. In our present study, we investigated the anti-neuroinflammatory effects and the possible mechanism of RKC-B1 in LPS-stimulated mice. After treatment with RKC-B1, RNA-seq transcriptome of the cerebral cortex tissue was conducted to find the differentially expressed genes (DEGs). Inflammatory cytokines and proteins were evaluated by ELISA and WB. In RNA-seq analysis, there were 193 genes screened as core genes of RKC-B1 for treatment with neuroinflammation. The significant KEGG enrichment signaling pathways of these core genes were mainly included TNF signaling pathway, IL-17 signaling pathway, NOD-like receptor signaling pathway, NF-κB signaling pathway and others. The corresponding top five KEGG enrichment pathways of three main clusters in PPI network of core genes were closely related to human immune system and immune disease. The results showed that RKC-B1 reduced the levels of pro-inflammatory factors (IL-6, IL-1β, MCP-1, and ICAM-1) and the expression of COX2 in cerebral cortex tissue. Additionally, we found that the anti-neuroinflammation activity of RKC-B1 might be related to suppress activating of NF-κB and NLRP3/cleaved caspase-1 signaling pathways. The current findings suggested that RKC-B1 might be a promising anti-neuroinflammatory agent.
RKC-B1 是一种从海洋小单孢菌 FIM02-523A 中获得的新型发酵产物。迄今为止，关于 RKC-B1 的药理学活性的报道很少。在本研究中，我们研究了 RKC-B1 在 LPS 刺激的小鼠中的抗神经炎症作用及其可能的机制。用 RKC-B1 处理后，对大脑皮质组织进行 RNA-seq 转录组分析，以寻找差异表达基因（DEGs）。通过 ELISA 和 WB 评估炎性细胞因子和蛋白质。在 RNA-seq 分析中，有 193 个基因被筛选为 RKC-B1 治疗神经炎症的核心基因。这些核心基因的显著 KEGG 富集信号通路主要包括 TNF 信号通路、IL-17 信号通路、NOD 样受体信号通路、NF-κB 信号通路等。核心基因 PPI 网络中三个主要簇的相应前五个 KEGG 富集通路与人类免疫系统和免疫性疾病密切相关。结果表明，RKC-B1 降低了大脑皮质组织中促炎因子（IL-6、IL-1β、MCP-1 和 ICAM-1）和 COX2 的表达水平。此外，我们发现 RKC-B1 的抗神经炎症活性可能与抑制 NF-κB 和 NLRP3/cleaved caspase-1 信号通路的激活有关。目前的研究结果表明，RKC-B1 可能是一种有前途的抗神经炎症药物。
