promote microglia M1 polarization through the NF-кB signaling pathway.

BACKGROUND

() is associated with the onset of Alzheimer's disease (AD), but the underlying molecular mechanism is unclear. Neuroinflammation in the brain from the microglial immune response induces the pathological progression of AD. In this study, the roles and molecular mechanism of in microglial inflammation were investigated.

METHODS

In this study, a oral administration mouse model was generated, and microglia were stimulated with . The viability of the microglia after treatment was evaluated through CCK-8 and live/dead cell staining. Inflammation in brain tissue after treatment and the immune response of microglia were detected by RT‒PCR, Western blotting and IF. Moreover, the RNA sequence was used, and the role of the NF-κB signalling pathway in microglial activation was analysed after stimulation.

RESULTS

The mRNA and protein levels of IL-6 and IL-17 were increased, and the expression of IL-10 was decreased in brain tissue after oral administration. The viability of the HMC3 cells significantly decreased with 5% after stimulation. The results of live/dead cell staining also showed the inhibitory effect of 5% supplementation on cell viability. Moreover, 5% supplementation increased the mRNA and protein levels of IL-6 and IL-17 and decreased IL-10 expression in HMC3 cells. supplementation increased the mRNA and protein levels of iNOS and CD86 and decreased CD206 expression in HMC3 cells. RNA sequencing revealed that the NF-κB signalling pathway was involved in this process. Furthermore, p-P65 was upregulated and p-IKBα was downregulated in brain tissue and HMC3 cells after stimulation, and an NF-κB signalling pathway inhibitor (QNZ) reversed the viability, M1 polarization and inflammatory factors of microglia in HMC3 cells .

CONCLUSIONS

In conclusion, induced neuroinflammation in the brain, possibly through promotion of M1 polarization of microglia via activation of the NF-κB signalling pathway during the progression of AD.