ArticleFrontiers in molecular neuroscience2018
Inhibitory Effects of Betulinic Acid on LPS-Induced Neuroinflammation Involve M2 Microglial Polarization via CaMKKβ-Dependent AMPK Activation.
Article in Frontiers in molecular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- Multitarget Actions of Pentacyclic Triterpenic Acids in Alzheimer's Disease: Mechanistic Insights.Molecules (Basel, Switzerland) · 2026Review
- Research advances in the application of betulinic acid for anti-inflammatory and anti-tumour therapy.Chinese medicine · 2026Review
- Review
- Mechanistic Insights into the Metabolic Pathways and Neuroprotective Potential of Pentacyclic Triterpenoids: In-Depth Analysis of Betulin, Betulinic, and Ursolic Acids.Biomolecules · 2025Review
- Paeonol Mitigates Neurodegeneration: Molecular Insights into Its Anti-inflammatory, Antioxidant, and Synaptoprotective Mechanisms.Molecular neurobiology · 2025Review
- Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Review
- Fluoride-induced Neurodevelopmental Toxicity- AMPK as a Possible Target.CNS & neurological disorders drug targets · 2025Review
- Article
- Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives.International journal of molecular sciences · 2024Review
- The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34.Nature communications · 2024Article
- Targeting AMP-activated protein kinase in sepsis.Frontiers in endocrinology · 2024Review
- Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review).International journal of molecular medicine · 2023Review
- Article
- Inflammation context in Alzheimer's disease, a relationship intricate to define.Biological research · 2022Review
- Arginine Reduces Glycation in γCells · 2022Article
- Anti-Inflammatory Activity of Panduratin A against LPS-Induced Microglial Activation.Biomedicines · 2022Article
- Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer's disease.Natural products and bioprospecting · 2022Article
- Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part II).International journal of molecular sciences · 2022Review
- A Novel Pyrazolo[3,4-Molecules and cells · 2022Article
- Microglia Polarization From M1 to M2 in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.