UM
Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKK beta-Dependent AMPK Activation
Li, Chuwen; Zhang, Chao; Zhou, Hefeng; Feng, Yu; Tang, Fan; Hoi, Maggie P. M.; He, Chengwei; Ma, Dan; Zhao, Chao; Lee, Simon M. Y.
2018-04-03
Source PublicationFRONTIERS IN MOLECULAR NEUROSCIENCE
ISSN1662-5099
Volume11
AbstractIn response to the microenvironment, microglia may polarize into either an M1 pro-inflammatory phenotype, exacerbating neurotoxicity, or an M2 anti-inflammatory phenotype, conferring neuroprotection. Betulinic acid (BA) is a naturally pentacyclic triterpenoid with considerable anti-inflammatory properties. Here, we aim to investigate the potential effects of BA on microglial phenotype polarization and to reveal the underlying mechanisms of action. First, we confirmed that BA promoted M2 polarization and inhibited M1 polarization in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Then, we demonstrated that the effect of BA on microglial polarization was dependent on AMP-activated protein kinase (AMPK) activation, as evidenced by the fact that both AMPK inhibitor compound C and AMPK siRNA abolished the M2 polarization promoted by BA. Moreover, we found that calmodulin-dependent protein kinase kinase beta (CaMKK beta), but not liver kinase B1, was the upstream kinase required for BA-mediated AMPK activation and microglial M2 polarization, via the use of both the CaMKK beta inhibitor STO-609 and CaMKK beta siRNA. Finally, BA enhanced AMPK phosphorylation and promoted M2 microglial polarization in the cerebral cortex of LPS-injected mice brains, which was attenuated by pre-administration of the AMPK inhibitor. This study demonstrated that BA promoted M2 polarization of microglia, thus conferring anti-neuroinflammatory effects via CaMKK beta-dependent AMPK activation.
KeywordAMP-activated protein kinase betulinic acid calmodulin-dependent protein kinase beta microglia polarization neuroinflammation
DOI10.3389/fnmol.2018.00098
URLView the original
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000429054100001
PublisherFRONTIERS MEDIA SA
The Source to ArticleWOS
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Citation statistics
Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Li, Chuwen,Zhang, Chao,Zhou, Hefeng,et al. Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKK beta-Dependent AMPK Activation[J]. FRONTIERS IN MOLECULAR NEUROSCIENCE,2018,11.
APA Li, Chuwen.,Zhang, Chao.,Zhou, Hefeng.,Feng, Yu.,Tang, Fan.,...&Lee, Simon M. Y..(2018).Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKK beta-Dependent AMPK Activation.FRONTIERS IN MOLECULAR NEUROSCIENCE,11.
MLA Li, Chuwen,et al."Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKK beta-Dependent AMPK Activation".FRONTIERS IN MOLECULAR NEUROSCIENCE 11(2018).
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