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Clinacanthus nutans Mitigates Neuronal Death and Reduces Ischemic Brain Injury: Role of NF-κB-driven IL-1β Transcription
- Source :
- NeuroMolecular Medicine. 23:199-210
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Neuroinflammation has been shown to exacerbate ischemic brain injury, and is considered as a prime target for the development of stroke therapies. Clinacanthus nutans Lindau (C. nutans) is widely used in traditional medicine for treating insect bites, viral infection and cancer, due largely to its anti-oxidative and anti-inflammatory properties. Recently, we reported that an ethanol extract from the leaf of C. nutans could protect the brain against ischemia-triggered neuronal death and infarction. In order to further understand the molecular mechanism(s) for its beneficial effects, two experimental paradigms, namely, in vitro primary cortical neurons subjected to oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery (MCA) occlusion, were used to dissect the anti-inflammatory effects of C. nutans extract. Using promoter assays, immunofluorescence staining, and loss-of-function (siRNA) approaches, we demonstrated that transient OGD led to marked induction of IL-1β, IL-6 and TNFα, while pretreatment with C. nutans suppressed production of inflammatory cytokines in primary neurons. C. nutans inhibited IL-1β transcription via preventing NF-κB/p65 nuclear translocation, and siRNA knockdown of either p65 or IL-1β mitigated OGD-mediated neuronal death. Correspondingly, post-ischemic treatment of C. nutans attenuated IκBα degradation and decreased IL-1β, IL-6 and TNFα production in the ischemic brain. Furthermore, IL-1β siRNA post-ischemic treatment reduced cerebral infarct, thus mimicking the beneficial effects of C. nutans. In summary, our findings demonstrated the ability for C. nutans to suppress NF-κB nuclear translocation and inhibit IL-1β transcription in ischemic models. Results further suggest the possibility for using C. nutans to prevent and treat stroke patients.
- Subjects :
- 0301 basic medicine
ved/biology
business.industry
ved/biology.organism_classification_rank.species
NF-κB
Pharmacology
In vitro
Clinacanthus nutans
Proinflammatory cytokine
03 medical and health sciences
Cellular and Molecular Neuroscience
IκBα
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
Neurology
chemistry
In vivo
Molecular Medicine
Medicine
Tumor necrosis factor alpha
business
030217 neurology & neurosurgery
Neuroinflammation
Subjects
Details
- ISSN :
- 15591174 and 15351084
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- NeuroMolecular Medicine
- Accession number :
- edsair.doi...........1decd18c6d158adcb10713b3d8124490