Abstract
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.
Highlights
Neuroinflammation has been widely researched and seems to be a common feature to central nervous system (CNS) diseases, such as ischemic stroke (IS) [1], traumatic brain injury (TBI) [2], Parkinson’s disease (PD) [3], Alzheimer’s disease (AD) [4] and temporal lobe epilepsy (TLE) [5,6]
To explore the core targets for RKC-B1 against neuroinflammation induced by LPS, RNA sequencing analysis was carried out between LPS model group and control group
Our results showed that LPS promoted the expression of COX2, while 10 mg/kg RKC-B1 reversed the increasing level of COX2 in the cerebral cortex tissue of LPS-induced mice
Summary
Neuroinflammation has been widely researched and seems to be a common feature to central nervous system (CNS) diseases, such as ischemic stroke (IS) [1], traumatic brain injury (TBI) [2], Parkinson’s disease (PD) [3], Alzheimer’s disease (AD) [4] and temporal lobe epilepsy (TLE) [5,6]. The activation of the neuroimmune cells, such as microglia and astrocytes, was one of the most characteristic events during the pathological process of neuroinflammation responses. In a recent study, researchers have found that the increasing of several neurosteroids in activated microglia had protective effects for neuron [8]. Aberrant inflammatory response was destructive to the health neurons in the brain through an increasing level of pro-inflammatory mediators, such as cytokines and ROS [9]
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