BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB
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-r...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-06-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00614/full |
| _version_ | 1818246218507091968 |
|---|---|
| author | Chuwen Li Tongkai Chen Tongkai Chen Hefeng Zhou Yu Feng Maggie P. M. Hoi Dan Ma Chao Zhao Ying Zheng Simon M. Y. Lee |
| author_facet | Chuwen Li Tongkai Chen Tongkai Chen Hefeng Zhou Yu Feng Maggie P. M. Hoi Dan Ma Chao Zhao Ying Zheng Simon M. Y. Lee |
| author_sort | Chuwen Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T14:45:19Z |
| format | Article |
| id | doaj.art-15867c7384ea4338892f45553f239a02 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T14:45:19Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-15867c7384ea4338892f45553f239a022022-12-22T00:21:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-06-01910.3389/fphar.2018.00614348449BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREBChuwen Li0Tongkai Chen1Tongkai Chen2Hefeng Zhou3Yu Feng4Maggie P. M. Hoi5Dan Ma6Chao Zhao7Ying Zheng8Simon M. Y. Lee9State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, ChinaInstitute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, ChinaDepartment of Clinical Neurosciences, Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, ChinaMicroglia-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.https://www.frontiersin.org/article/10.3389/fphar.2018.00614/fullBHDPCneuroinflammationmicrogliaNF-κBCREBPKA |
| spellingShingle | Chuwen Li Tongkai Chen Tongkai Chen Hefeng Zhou Yu Feng Maggie P. M. Hoi Dan Ma Chao Zhao Ying Zheng Simon M. Y. Lee BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB Frontiers in Pharmacology BHDPC neuroinflammation microglia NF-κB CREB PKA |
| title | BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB |
| title_full | BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB |
| title_fullStr | BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB |
| title_full_unstemmed | BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB |
| title_short | BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB |
| title_sort | bhdpc is a novel neuroprotectant that provides anti neuroinflammatory and neuroprotective effects by inactivating nf κb and activating pka creb |
| topic | BHDPC neuroinflammation microglia NF-κB CREB PKA |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00614/full |
| work_keys_str_mv | AT chuwenli bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT tongkaichen bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT tongkaichen bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT hefengzhou bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT yufeng bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT maggiepmhoi bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT danma bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT chaozhao bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT yingzheng bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb AT simonmylee bhdpcisanovelneuroprotectantthatprovidesantineuroinflammatoryandneuroprotectiveeffectsbyinactivatingnfkbandactivatingpkacreb |