UM
Inhibitory effects of betulinic acid on LPS-induced neuroinflammation involve M2 microglial polarization via CaMKKβ-dependent AMPK activation
Li C.3; Zhang C.3; Zhou H.3; Feng Y.3; Tang F.3; Hoi M.P.M.3; He C.3; Ma D.1; Zhao C.1; Lee S.M.Y.3
2018-04-03
Source PublicationFrontiers in Molecular Neuroscience
ISSN16625099
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 β (CaMKKβ), 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 CaMKKb inhibitor STO-609 and CaMKKβ siRNA. Finally, BA enhanced AMPK phosphorylation and promoted M2 microglial polarization in the cerebral cortex of LPSinjected 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 CaMKKβ-dependent AMPK activation.
KeywordAMP-activated protein kinase Betulinic acid Calmodulin-dependent protein kinase β Microglia polarization Neuroinflammation
DOI10.3389/fnmol.2018.00098
URLView the original
Language英語
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Cited Times [WOS]:15   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute
2.Beijing University of Chinese Medicine
3.University of Macau
First Author AffilicationUniversity of Macau
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GB/T 7714
Li C.,Zhang C.,Zhou H.,et al. Inhibitory effects of betulinic acid on LPS-induced neuroinflammation involve M2 microglial polarization via CaMKKβ-dependent AMPK activation[J]. Frontiers in Molecular Neuroscience,2018,11.
APA Li C..,Zhang C..,Zhou H..,Feng Y..,Tang F..,...&Lee S.M.Y..(2018).Inhibitory effects of betulinic acid on LPS-induced neuroinflammation involve M2 microglial polarization via CaMKKβ-dependent AMPK activation.Frontiers in Molecular Neuroscience,11.
MLA Li C.,et al."Inhibitory effects of betulinic acid on LPS-induced neuroinflammation involve M2 microglial polarization via CaMKKβ-dependent AMPK activation".Frontiers in Molecular Neuroscience 11(2018).
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