RKC-B1 Blocks Activation of NF-κB and NLRP3 Signaling Pathways to Suppress Neuroinflammation in LPS-Stimulated Mice

• Published in: Marine drugs 2021-07, Vol.19 (8), p.429
• Main Authors: Liu, Man, Yang, Ying-Lin, Zhang, Shan-Shan, Liu, Dong-Ni, Fang, Lian-Hua, Du, Guan-Hua, Wang, Yue-Hua
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; Anti-Inflammatory Agents - pharmacology; Aquatic Organisms; Caspase-1; Cerebral cortex; Chemokines; Cyclooxygenase-2; Cytokines; Disease Models, Animal; ELISA; Enrichment; Fermentation; Genes; IL-1β; Immune system; Immunity; Immunological diseases; Infectious diseases; Inflammation; Intercellular adhesion molecule 1; Interleukin 17; Interleukin 6; lipopolysaccharide (LPS); Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Microglia; Monocyte chemoattractant protein 1; neuroinflammation; Neuroinflammatory Diseases - chemically induced; Neuroinflammatory Diseases - drug therapy; NF-kappa B - metabolism; NF-κB; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Phosphorylation; Protein expression; Proteins; Receptors; Ribonucleic acid; RKC-B1; RNA; Signal transduction; Signal Transduction - drug effects; Signaling; Tissue; Transcriptomes; Traumatic brain injury; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 1660-3397; 1660-3397
• 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.