BHDPC is a novel neuroprotectant that provides anti-neuroinflammatory and neuroprotective effects by inactivating NF-κB and activating PKA/CREB

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 l 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-κB) via interfering with the degradation of the inhibitor of kappa B (IκB) and phosphorylation of IκB, the IκB 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.

Publication DOI: https://doi.org/10.3389/fphar.2018.00614
Divisions: College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
Additional Information: Funding Information: This study was supported by grants from The Science and Technology Development Fund (FDCT) of Macao SAR (Nos. 069/2015/A2, 134/2014/A3, and 017/2015/AMJ) and the Research Committee of the University of Macau (MYRG2016-00129-ICMS-QRCM, MYRG2016-00133-ICMS-QRCM, MYRG2015-00214-ICMSQRCM, and MYRG2015-00182-ICMS-QRCM). © 2018 Li, Chen, Zhou, Feng, Hoi, Ma, Zhao, Zheng and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Uncontrolled Keywords: BHDPC,CREB,Microglia,Neuroinflammation,NF-κB,PKA,Pharmacology,Pharmacology (medical)
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.fro ... 2018.00614/full (Publisher URL)
PURE Output Type: Article
Published Date: 2018-06-25
Accepted Date: 2018-05-22
Authors: Li, Chuwen
Chen, Tongkai
Zhou, Hefeng
Feng, Yu
Hoi, Maggie P.M.
Ma, Dan (ORCID Profile 0000-0001-8628-8954)
Zhao, Chao
Zheng, Ying
Lee, Simon M.Y.

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