Curcumin Inhibits LPS-Induced Neuroinflammation by Promoting Microglial M2 Polarization via TREM2/TLR4/NF-Κb Pathways in BV2 Cells
Abstract
Microglia mediate multiple facets of neuroinflammation, which plays a double-edged role in various brain diseases via distinct microglial phenotypes (deleterious M1 and neuroprotective M2). Therefore, the inhibition of overactivated inflammatory M1 microglia by switching to the protective M2 phenotype appears to be a potential therapeutic strategy in neuroinflammatory disorders. Curcumin has been shown to exhibit anti-inflammatory and neuroprotective activities. The present study investigated the potential effects of curcumin on microglial M1/M2 polarization and elucidated the possible molecular mechanisms of action in vitro. In this study, the BV2 microglial cell line was pretreated with different curcumin concentrations in the presence or absence of lipopolysaccharide (LPS) to assess the anti-inflammatory efficacy of curcumin based on the morphological and inflammatory changes. The cytotoxicity of curcumin for BV2 cells was evaluated using the CCK-8 assay. Further, the effect of curcumin concentrations on LPS-induced BV2 cells was studied. The morphological changes were observed using an optical microscope and immunofluorescent staining. Nitric oxide (NO) expression was determined using the Griess reagent. The expression of cytokines and inflammatory mediators was also measured by ELISA, qRT-PCR, flow cytometry, and immunofluorescence. Western blot analysis was used to determine the levels of triggering receptor expressed on myeloid cells 2 (TREM2), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) p65, p-NF-κB p65, IκB, and p-IκB expression. Results showed that curcumin concentrations less than 10 μM did not induce any detectable cytotoxicity but decreased BV2 cell viability up to 20 μM. Curcumin inhibited LPS-induced microglial activation. Curcumin treatment switched the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype by decreasing the expression of M1 markers (i.e., iNOS, IL-1β, IL-6, and CD16/32) and elevating the expression of M2 markers (i.e., arginase 1, IL-4, IL-10, and CD206). Interestingly, curcumin attenuated the activation of TLR4/NF-κB pathways and the downregulation of TREM2 expression in LPS-activated BV2 cells. Collectively, these results suggest that curcumin significantly alleviates LPS-induced inflammation by regulating microglial (M1/M2) polarization by reducing the imbalance of TREM2 and TLR4 and balancing the downstream NF-κB activation.
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Curcumin inhibits NF-κB and MAPK activation in LPS-stimulated microglia.
“curcumin has been demonstrated to inhibit NF-κB and MAPK activation in LPS-stimulated microglia (Porro et al., 2019; Zhang et al., 2019)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Zhang et al., 2019
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- Authors
- Zhang, J., Zheng, Y., Luo, Y., Du, Y., Zhang, X., & Fu, J.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Fu, Jianliang
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 116
- Pages
- 29-37
- ISSN
- 0161-5890 (ISSN-L)
- OpenAlex
- W2977662739
- Cited by
- 464
- References
- 45
- Citations by year
- 2026: 60 · 2025: 75 · 2024: 77 · 2023: 99 · 2022: 83 · 2021: 48 · 2020: 22
- FWCI
- 16.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Innovative Research Group Project of the National Natural Science Foundation of China
- National Natural Science Foundation of China (81871103, 81672243)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- curcumin, neuroinflammation, microglial polarization, M2 microglia, M1 microglia, lipopolysaccharide, TREM2, TLR4, NF-κB signaling, BV2 microglial cells, anti-inflammatory activity, nitric oxide, cytokines, neuroprotection, neurodegenerative diseases, cytotoxicity
- MeSH terms
- Animals, Cell Line, Curcumin, Inflammation, Lipopolysaccharides, Membrane Glycoproteins, Phenotype, Receptors, Immunologic, Signal Transduction, Biomarkers, Down-Regulation, NF-kappa B, Cell Polarity, Microglia, Toll-Like Receptor 4, Mice
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