Abstract
Objectives
Chronic neuroinflammation has become one of the important causes of common neurodegeneration disease. Therefore, the target of this study was to explore the protective action of glabridin on lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro and its mechanism.
Methods
The neuroinflammation model was established by LPS-induced BV2 cells. The cell viability with various concentrations of glabridin was determined by MTT assay, and the content of NO in each group was detected. A neuroinflammatory model was established in male C57BL/6J mice for a water maze test. Subsequently, NF-κB and SOD indices were measured by ELISA, GFAP and IBA-1 indices were measured by immunofluorescence, and Nissl staining was used to explore the Nissl bodies in the hippocampus of mice.
Results
In vitro experiments, our results expressed that glabridin could markedly increase the cell activity of LPS-induced BV2 cells and reduce the NO expression in cells. It indicated that glabridin had a remarkable impact on the neuroinflammation of LPS-induced BV2 cell protection. In vivo neuroinflammation experiments, mice treated with different doses of glabridin showed significantly improved ability of memory compared with the LPS group in the Morris water maze test. The levels of NF-κB, GFAP, and the number of positive cells in Nissl staining were decreased. High-dose glabridin significantly increased the SOD content in the brain tissue and decreased the IBA-1 levels.
Conclusion
Glabridin can significantly reduce or even reverse LPS-induced neuroinflammation, which may be related to the fact that glabridin can reduce the NO expression, NF-κB, IBA-1, GFAP, and other inflammatory mediators, upregulate the expression of SOD to relieve oxidative stress of brain and inhibit the activation of gliocyte in brain tissue.
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Abbreviations
- LPS:
-
Lipopolysaccharide
- MTT:
-
Methyl-thiazolyl-tetrazolium
- NO:
-
Nitric oxide
- NF-κB:
-
Nuclear factor kappa-B
- SOD:
-
Superoxide dismutase
- ELISA:
-
Enzyme-linked immunosorbent assay
- TTP488:
-
Azeliragon
- GFAP:
-
Glial fibrillary acidic protein
- IBA-1:
-
Ionized calcium-binding adapter molecule 1
- DG:
-
Dentate gyrus
- CA1:
-
Glutamine 1
- CY3:
-
Cyanine3
- FITC:
-
Fluorescein Isothiocyanate
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Acknowledgements
This work was funded by the Guangdong Provincial Key Laboratory of Plant Resources Biorefinery (No. 2021GDKLPRB02) and the Basic and Applied Basic Research Foundation of Guangdong Province (No. 2020A1515110715).
Funding
Guangdong Provincial Key Laboratory of Plant Resources Biorefinery, 2021GDKLPRB02, Lanyue Zhang, the Basic and Applied Basic Research Foundation of Guangdong Province, 2020A1515110715, Lanyue Zhang
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JW: Research, digitize and write the first draft. YW: Research, digitize and write the first draft. ZT: Digitize, investigation and verification. YY: Data collation. SH: Investigation. ZL: Formal analysis. YL: Data collation and modification. LZ: Conceptualization, supervision, resources and capital acquisition. ZD: Conceptualization, methodology, supervision, review and proofreading.
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All animal experiments are conducted in accordance with relevant government and institutional regulations on the ethical use of animals and are approved by the Experimental Animal Center of Guangdong Province (approval documents: SCXK/20130002).
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Weng, J., Wang, Y., Tan, Z. et al. Glabridin reduces neuroinflammation by modulating inflammatory signals in LPS-induced in vitro and in vivo models. Inflammopharmacol 32, 1159–1169 (2024). https://doi.org/10.1007/s10787-023-01424-5
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DOI: https://doi.org/10.1007/s10787-023-01424-5