Betulinic Acid Inhibits LPS-Induced MMP-9 Expression by Suppressing NF-kB Activation in BV2 Microglial Cells

Kim, Sung‐Soo

doi:10.4062/biomolther.2011.19.4.431

Cited by 8 publications

(5 citation statements)

References 38 publications

(41 reference statements)

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“…BA is a widely used natural product and its anti-inflammatory properties are well known ( Saaby and Nielsen, 2012 ; Wan et al, 2013 ; Ju et al, 2015 ; Lingaraju et al, 2015 ; Kim et al, 2016 ; Laavola et al, 2016 ). Moreover, BA was able to decrease pro-inflammatory cytokine release and matrix metalloproteinase expression in LPS-stimulated microglial cells, indicating a definite anti-neuroinflammatory role of BA in CNS ( Lee et al, 2011 ; Wan et al, 2013 ). Therefore, it is of significance to test the role of BA in the regulation of microglia polarization, and to further explore the possible molecular mechanisms.…”

Section: Discussionmentioning

confidence: 94%

“…This compound has been reported to possess various kinds of biological properties, including anti-inflammatory, anticancer, antimalarial, and antiplatelet activities, etc. ( Lee et al, 2011 ; Wan et al, 2013 ; Jingbo et al, 2015 ; Ju et al, 2015 ; Lingaraju et al, 2015 ; Kim et al, 2016 ; Laavola et al, 2016 ). The anti-inflammatory effect of BA is well recognized in several different models ( Saaby and Nielsen, 2012 ; Wan et al, 2013 ; Ju et al, 2015 ; Lingaraju et al, 2015 ; Kim et al, 2016 ; Laavola et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…Also, BA was found to suppress inflammation via activation of PPAR-γ in human osteoarthritis chondrocytes ( Jingbo et al, 2015 ). In addition, BA was reported to decrease LPS-induced matrix metalloproteinase-9 expression via blocking the nuclear translocation of nuclear factor-κB in microglial cells ( Lee et al, 2011 ; Wan et al, 2013 ). Recently, several reports also demonstrated that BA could activate AMPK pathways in vitro and in vivo ( Jin et al, 2016 ; Silva et al, 2016 ; Xie et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKKβ-Dependent AMPK Activation

Zhang

Zhou

et al. 2018

Front. Mol. Neurosci.

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In 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 CaMKKβ inhibitor STO-609 and CaMKKβ 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 CaMKKβ-dependent AMPK activation.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKKβ-Dependent AMPK Activation

Zhang

Zhou

et al. 2018

Front. Mol. Neurosci.

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“…In response to various microenvironments, microglia can polarise into pro-and anti-inflammatory phenotypes [9,10]. Moreover, more remarkably, activation of Nrf2 pathways has been shown to promote microglial polarisation toward the anti- [27][28][29]. On the other hand, Nrf2-deficiency is reported to be more important in inflammatory models [10].…”

Section: Discussionmentioning

confidence: 99%

Schisantherin A Attenuates Neuroinflammation in Activated Microglia: Role of Nrf2 Activation Through ERK Phosphorylation

Chen

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the present study, we investigated whether schisantherin A (StA) had anti-inflammatory effects under neuroinflammatory conditions. Methods: The effects of StA and its underlying mechanisms were examined in lipopolysaccharide (LPS)-activated BV-2 microglial cells by ELISA, qPCR, EMSA, Western blot, and IHC. Results: Firstly, we found that StA inhibited the inflammatory response in LPS-activated BV-2 microglia. Secondly, we found that StA suppressed LPS-induced activation of NF-κB via interfering with degradation of IκB and phosphorylation of IκB, IKK, PI3K/Akt, JNK, and p38 MAPK. Thirdly, StA conferred indirect antioxidative effects via quenching ROS and promoted expression of antioxidant enzymes, including HO-1 and NQO-1, via stimulating activation of Nrf2 pathways. Finally, we demonstrated that anti-neuroinflammatory actions of StA were dependent on ERK phosphorylation-mediated Nrf2 activation. Conclusion: StA induced ERK phosphorylation-mediated Nrf2 activation, which contributed to its anti-inflammation and anti-oxidation. The anti-neuroinflammatory and anti-oxidative effects of StA may show preventive therapeutic potential for various neuroinflammatory disorders.

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“…Betulinic acid was shown to have anti-inflammatory effects by suppressing LPS-induced NO production as well as TNF-α and IL-1β secretion in microglial cell (Lee et al, 2011a). It was shown that β-sitosterol negatively regulates pro-inflammatory cytokines by inhibiting STAT1 and NF-κB pathways (Valerio and Awad, 2011).…”

Section: Effects Of Several Compounds On the Production Of Inflammatomentioning

confidence: 97%

Methanol extracts of Xanthium sibiricum roots inhibit inflammatory responses via the inhibition of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) in murine macrophages

Cho

2015

Journal of Ethnopharmacology

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Betulinic Acid Inhibits LPS-Induced MMP-9 Expression by Suppressing NF-kB Activation in BV2 Microglial Cells

Cited by 8 publications

References 38 publications

Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKKβ-Dependent AMPK Activation

Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKKβ-Dependent AMPK Activation

Schisantherin A Attenuates Neuroinflammation in Activated Microglia: Role of Nrf2 Activation Through ERK Phosphorylation

Methanol extracts of Xanthium sibiricum roots inhibit inflammatory responses via the inhibition of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) in murine macrophages

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