Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation

Introduction: Nucleotide-binding and oligomerization domain like receptors protein 3 (NLRP3) inflammasome-mediated interleukin (IL)-1 beta secretion plays an important role in the progression of Alzheimer's disease (AD). Curcumin has been shown to improve cognitive impairment and learning ability of AD mice by reducing IL-1 beta secretion. However, its exact mechanism of action remains unclear. In the present study, we explored the relationship between the neuroprotective effect of curcumin and activation of the NLRP3 inflammasome pathway. Methods: BV2 cells were primed with 500 ng/mL lipopolysaccharide (LPS) for 4 h and subsequently treated with 50 mu M A beta(25-35) for 24 h or pretreated with 2.5-10 mu M curcumin for 4 h and exposed to 50 mu M A beta(25-35) for 24 h. The effects of curcumin and A beta(25-35) were assessed by the CCK8 assay. ELISA was used for the detection of IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha levels in the supernatant of the cell culture medium. The viability of SH-SYSY cells, which were incubated with conditioned medium (CM) was assessed using the CCK8 assay. The percentage of apoptotic SH-SYSY cells incubated with CM was assessed using Annexin V-FITC/PI staining flow cytometry analysis. The expression levels of NLRP3, caspase- I and IL-1 beta were observed by western blot and immunofluorescence staining analyses; the mRNA levels of nlrp3, caspase-I and IL-1 beta were analyzed using qRT-PCR. Results: Low (2.5 mu M), medium (5 mu M), and high (10 mu M) concentrations of curcumin and 50 mu M A beta(25-35) were used to perform the experiments in the present study. Curcumin attenuated the IL-1 beta, IL-6, and TNF-alpha release and increased SHSYSY cell activity, while decreasing the apoptotic percentage of SH-SYSY cells using A beta(25-35) for cell stimulation (p < 0.05). Furthermore, curcumin inhibited the expression of NLRP3, caspase-1 and IL-1 beta and nlrp3 in BV-2 cells (p < 0.05), However, curcumin did not affect the expression levels of caspase-1 and IL-1 beta (p > 0.05) Conclusion: Overall, the data indicated that curcumin is a promising neuroprotective agent for suppressing neuro-inflammation by inhibiting the NLRP3 inflammasome pathway.