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BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-kappa B and Activating PKA/CREB
Li, Chuwen1; Chen, Tongkai1,2; Zhou, Hefeng1; Feng, Yu1; Hoi, Maggie P. M.1; Ma, Dan3; Zhao, Chao3; Zheng, Ying1; Lee, Simon M. Y.1
2018-06-25
Source PublicationFRONTIERS IN PHARMACOLOGY
ISSN1663-9812
Volume9
Abstract

Microglia-mediated neuroinflammatory responses are inevitable and important pathological processes in several kinds of disorder of the central nervous system (CNS). Therefore, alleviating activated microglia-induced inflammatory process might be a valuable therapeutic approach to neuroinflammation-related diseases. In the present study, we investigated BHDPC, a novel neuroprotectant discovered in our previous study that had anti-inflammatory effects under neuroinflammatory conditions. First, we found that BHDPC could inhibit neuroinflammatory responses and promote microglial M2 phenotype polarization in both lipopolysaccharide (LPS)-activated BV-2 microglia I cells. Furthermore, BHDPC provided protective actions against neuroinflammation-induced neurotoxicity in HT22 mouse hippocampal cells co-cultured with activated BV-2 microglia. Further experiments demonstrated that BHDPC could suppress LPS-induced activation of transcription factor nuclear factor kappa B (NF-kappa B) via interfering with the degradation of the inhibitor of kappa B (I kappa B) and phosphorylation of I kappa B, the I kappa B kinase (IKK). Moreover, we also found that BHDPC could induce phosphorylation of cAMP-dependent protein kinase A (PKA) and cAMP-response element-binding protein (CREB) in BV-2 microglial cells. Also, using the PKA-specific inhibitor, we found that BHDPC-induced CREB phosphorylation was dependent on PKA, which also contributed to BHDPC-mediated anti-inflammation and neuroprotection.

KeywordBhdpc Neuroinflammation Microglia Nf-kappa b Creb Pka
DOIhttps://doi.org/10.3389/fphar.2018.00614
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000436109800001
PublisherFRONTIERS MEDIA SA
The Source to ArticleWOS
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Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLee, Simon M. Y.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
2.Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China
3.Department of Clinical Neurosciences, Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Li, Chuwen,Chen, Tongkai,Zhou, Hefeng,et al. BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-kappa B and Activating PKA/CREB[J]. FRONTIERS IN PHARMACOLOGY,2018,9.
APA Li, Chuwen.,Chen, Tongkai.,Zhou, Hefeng.,Feng, Yu.,Hoi, Maggie P. M..,...&Lee, Simon M. Y..(2018).BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-kappa B and Activating PKA/CREB.FRONTIERS IN PHARMACOLOGY,9.
MLA Li, Chuwen,et al."BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-kappa B and Activating PKA/CREB".FRONTIERS IN PHARMACOLOGY 9(2018).
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