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Chinese Journal of Cell and Stem Cell(Electronic Edition) ›› 2024, Vol. 14 ›› Issue (04): 193-203. doi: 10.3877/cma.j.issn.2095-1221.2024.04.001

• Original Research •    

Curcumin alleviates LPS-induced neuroinflammatory damage of microglia by regulating the NF-κB/NLRP3 pathway

Jiacui Ji1, Chunbin Sun2, Enli Luo3,()   

  1. 1. Shandong Mental Health Center, Jinan 250014, China
    2. School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
    3. Second Department of Traditional Chinese Medicine, South China Hospital, Shenzhen University, Shenzhen 518116, China
  • Received:2024-02-07 Online:2024-08-01 Published:2024-08-14
  • Contact: Enli Luo

Abstract:

Objective

To investigatethe inhibitory effect and mechanisms of curcumin on lipopolysaccharide (LPS) -induced inflammation of nerve cells.

Methods

Microglia (BV2) was used in current study and named control group (without any treatment), model group (treated with LPS 100 ng/mL for 24 h) and treatment group (curcumin at 1, 5, 10 μmol/L concentration plus 100 ng/ml LPS for 24 h). The expression levels of interleukin-6 (IL-6), IL-10, p-NF-κB, NLRP3, Bax and Bcl-2 in BV2 cells were detected by immunofluorescence assay. Western blot was used to detect the protein expression of NF-κB/NLRP3 signaling pathway. The contents of tumor necrosis factor α (TNF-α), IL-1β and iNOS were detected by ELISA. In addition, the expression levels of IL-6, IL-10, Bax and Bcl-2 proteins in BV2 cells were detected after administration of NF-κB inhibitor BAY 11-7082. The experimental data were analyzed by t test, one-way ANOVA and Dunnett-t test.

Results

Compared with the control group, the inflammatory cytokines TNF-α (398.80 ± 11.39 vs 113.00 ± 5.93), IL-1β (592.40 ± 11.32 vs 206.70 ± 6.81), IL-6 (1.73 ± 0.09 vs 0.99 ± 0.03), iNOS (88.39 ± 2.14 vs 32.48 ± 1.71), p-NF-κB (1.92 ± 0.02 vs 1.02 ± 0.05), INOS (88.39 ± 2.14 vs 32.48 ± 1.71), NLRP3 (10.33 ± 0.61 vs 1.02 ± 0.05) and apoptosis-related protein Bax (2.68 ± 0.10 vs 1.05 ± 0.08) in the model group were increased. IL-10 (0.82 ± 0.03 vs 1.01 ± 0.06) and Bcl-2 protein expression levels (0.70 ± 0.02 vs 1.11 ± 0.06) were decreased (P < 0.05). Western blot results showed that compared with the control group, the protein expression levels of p-NF-κB (2.65 ± 0.06 vs 1.04 ± 0.05) and NLRP3 (4.38 ± 0.08 vs 1.07 ± 0.04) in the model group were increased (P < 0.001). Compared to the model group, the expression levels of TNF-α (207.90 ± 7.37 vs 398.80 ± 11.39), IL-1β (405.40 ± 6.56 vs 592.40 ± 11.32), IL-6 (1.09 ± 0.05 vs 1.73 ± 0.09), iNOS (39.52 ± 1.32 vs 88.39 ± 2.14), p-NF-κB (01.21 ± 0.05 vs 1.92 ± 0.02) and NLRP3 (1.51 ± 0.11 vs 10.33 ± 0.61) were decreased, and the expression levels of IL-10 (2.61 ± 0.03 vs 0.82 ± 0.03) were increased after treatment with high concentration of curcumin. Compared with the model group, the expression level of Bax protein was decreased (0.80 ± 0.04 vs 2.68 ± 0.10), while the expression level of Bcl-2 protein was increased after high concentration curcumin treatment (1.93 ± 0.02 vs 0.70 ± 0.02) (P < 0.001). Compared with the model group, the expression levels of IL-6 (0.88 ± 0.06 vs 2.70 ± 0.12) and Bax protein (1.14 ± 0.04 vs 3.63 ± 0.16) were decreased, while the expression levels of IL-10 (1.58 ± 0.03 vs 0.52 ± 0.04) and Bcl-2 protein (1.48 ± 0.11 vs 0.53 ± 0.05) were increased after NF-κB inhibitor treatment (P < 0.001). Western blot results showed that compared with the model group, the expression levels of p-NF-κB and NLRP3 protein were decreased after curcumin treatment with 1, 5 and 10 μmol/L concentration in dose-dependent manner (0.40 ± 0.02 vs 2.65 ± 0.06, 0.21 ± 0.02 vs 4.38 ± 0.08, P < 0.001) .

Conclusion

Curcumin could reduce LPS-induced neuroinflammatory damage in microglia, and its mechanism may be related to down-regulating NF-κB/NLRP3 signaling pathway, inhibiting inflammation and apoptosis.

Key words: Curcumin, NF-κB/NLRP3 signaling pathway, Inflammatory damage, Apoptosis

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