Anti-inflammatory effects of B vitamins protect against tau hyperphosphorylation and cognitive impairment induced by 1,2 diacetyl benzene: An in vitro and in silico study

Abstract

1,2 diacetyl benzene (DAB) penetrates the blood-brain barrier, causing neuroinflammation, tau hyperphosphorylation, and cognitive impairment. Converging evidence supports the anti-inflammatory effects of B vitamins on cognitive impairment, but the effects of B vitamins on cognitive impairment induced by DAB remain unclear. Here, we investigated the anti-inflammatory properties of B vitamins in DAB-stimulated human neuroblastoma SH-SY5Y cells. In this in-silico analysis, we investigated the genes, transcription factors, miRNAs, and sponges linked with DAB, B vitamins and the pathogenesis of cognitive impairment. We found vitamins B1, B2, and B3 had anti-inflammatory properties in DAB-stimulated SH-SY5Y cells, possibly via inhibiting NF-κB activation. Furthermore, vitamins B1, B2, and B3 inhibited GSK-3β, β-amyloid, and tau hyperphosphorylation in SH-SY5Y cells. These vitamins can also modulate genes induced by DAB (IL1B, IL6, IL10, iNOS, COX2, NFκB, GSK3B, TNF, and APP) in SH-SY5Y cells. In silico analyses, inflammatory response related pathways, "Alzheimer's disease", "pathways of neurodegeneration-multiple disease", and "prolactin signaling pathway", were highlighted. Additionally, we explored a network-based approach to identify key genes, transcription factors, miRNAs, and pathways in cognitive impairment. The transcription factors NFKB2 and BATF3 were shown to be the most important in regulating genes. We also found eight significant miRNAs related to cognitive impairment, and these miRNAs were also validated by qPCR. Finally, we developed and tested in silico miRNA sponge sequences for these miRNAs.

Keywords: 1,2 diacetyl benzene; B vitamins; Cognitive impairment; Genes; Molecular mechanisms; miRNAs.