- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Faculty Research and Publications /
- Natural Compounds Oridonin and Shikonin Exhibit Potentially...
Open Collections
UBC Faculty Research and Publications
Natural Compounds Oridonin and Shikonin Exhibit Potentially Beneficial Regulatory Effects on Select Functions of Microglia Greuel, Bridget K.; Da Silva, Dylan E.; Robert-Gostlin, Victoria N.; Klegeris, Andis
Abstract
Accumulating evidence indicates that the adverse neuroimmune activation of microglia, brain immunocytes that support neurons, contributes to a range of neuroinflammatory disorders, including Alzheimer’s disease. Correcting the abnormal functions of microglia is a potential therapeutic strategy for these diseases. Nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor (NLRP) 3 inflammasomes are implicated in adverse microglial activation and their inhibitors, such as the natural compounds oridonin and shikonin, reduce microglial immune responses. We hypothesized that some of the beneficial effects of oridonin and shikonin on microglia are independent of their suppression of NLRP3 inflammasomes. Murine and human microglia-like cells were stimulated with bacterial lipopolysaccharide (LPS) only, which did not induce NLRP3 inflammasome activation or the resulting secretion of interleukin (IL)-1β, allowing for the identification of other anti-inflammatory effects. Under these experimental conditions, both oridonin and shikonin reduced nitric oxide (NO) secretion and the cytotoxicity of BV-2 murine microglia towards HT-22 murine neuronal cells, but upregulated BV-2 cell phagocytic activity. Only oridonin inhibited the secretion of tumor necrosis factor (TNF) by stimulated BV-2 microglia, while only shikonin suppressed the respiratory burst response of human HL-60 microglia-like cells. This observed discrepancy indicates that these natural compounds may have different molecular targets in microglia. Overall, our results suggest that oridonin and shikonin should be further investigated as pharmacological agents capable of correcting dysfunctional microglia, supporting their potential use in neuroinflammatory disorders.
Item Metadata
Title |
Natural Compounds Oridonin and Shikonin Exhibit Potentially Beneficial Regulatory Effects on Select Functions of Microglia
|
Creator | |
Publisher |
Multidisciplinary Digital Publishing Institute
|
Date Issued |
2024-03-28
|
Description |
Accumulating evidence indicates that the adverse neuroimmune activation of microglia, brain immunocytes that support neurons, contributes to a range of neuroinflammatory disorders, including Alzheimer’s disease. Correcting the abnormal functions of microglia is a potential therapeutic strategy for these diseases. Nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor (NLRP) 3 inflammasomes are implicated in adverse microglial activation and their inhibitors, such as the natural compounds oridonin and shikonin, reduce microglial immune responses. We hypothesized that some of the beneficial effects of oridonin and shikonin on microglia are independent of their suppression of NLRP3 inflammasomes. Murine and human microglia-like cells were stimulated with bacterial lipopolysaccharide (LPS) only, which did not induce NLRP3 inflammasome activation or the resulting secretion of interleukin (IL)-1β, allowing for the identification of other anti-inflammatory effects. Under these experimental conditions, both oridonin and shikonin reduced nitric oxide (NO) secretion and the cytotoxicity of BV-2 murine microglia towards HT-22 murine neuronal cells, but upregulated BV-2 cell phagocytic activity. Only oridonin inhibited the secretion of tumor necrosis factor (TNF) by stimulated BV-2 microglia, while only shikonin suppressed the respiratory burst response of human HL-60 microglia-like cells. This observed discrepancy indicates that these natural compounds may have different molecular targets in microglia. Overall, our results suggest that oridonin and shikonin should be further investigated as pharmacological agents capable of correcting dysfunctional microglia, supporting their potential use in neuroinflammatory disorders.
|
Subject | |
Genre | |
Type | |
Language |
eng
|
Date Available |
2024-04-26
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
CC BY 4.0
|
DOI |
10.14288/1.0441982
|
URI | |
Affiliation | |
Citation |
Brain Sciences 14 (4): 328 (2024)
|
Publisher DOI |
10.3390/brainsci14040328
|
Peer Review Status |
Reviewed
|
Scholarly Level |
Faculty; Researcher
|
Rights URI | |
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
CC BY 4.0