The anti-inflammatory effects of vitamin B6 on neuroinflammation and neuronal damage caused by 1,2-diacetylbenzene in BV2 microglial and sH-SY5Y cells.

Abstract

Background: The pathophysiology of cognitive impairment has recently focused on 1,2-Diacetylbenzene (DAB), B vitamins, tau hyperphosphorylation, and neuroinflammation. While past evidence shows that vitamin B6 influences the immune system, the molecular processes behind DAB-induced neuroinflammation and cognitive impairment remain largely unknown. This study aimed to assess the protective roles of vitamin B6 against DAB-induced toxicity in BV2 microglial and SH-SY5Y cells.

Methods: In vitro approaches included Western blot, qRT-PCR, cell viability assays, immunocytochemistry, reactive oxygen species, and nitrite assays. For in silico analysis, we utilized Metascape, Cytoscape, MIENTURNET, and molecular docking.

Results: Vitamin B6 suppressed the TLR4/NF-κB pathway and the TREM-1/DAP12/NLRP3/caspase-1/IL1B pathway in DAB-activated BV2 cells. Additionally, it reduced reactive oxygen species and nitric oxide levels while increasing Nrf2 and IL10 production. In SH-SY5Y cells, vitamin B6 inhibited GSK-3β Tyr216, tau hyperphosphorylation, and β-amyloid production. The in silico analysis identified 'positive regulation of NF-κB transcription factor activity,' 'regulation of IL-6 production,' and 'positive regulation of adaptive immune response' as key molecular mechanisms linked with DAB-induced cognitive impairment and targeted by vitamin B6. Core genes, miRNAs, and transcription factors included IL1β, IL6, IL10, TNF, hsa-miR-155-5p, hsa-miR-203a-3p, hsa-miR-106a-5p, hsa-miR-26a-5p, CEBPB, and PXR.

Conclusion: Our findings indicate that vitamin B6 may protect against DAB-induced cognitive impairment by attenuating key inflammatory pathways, reducing oxidative stress, and inhibiting tau hyperphosphorylation, β-amyloid production, and GSK-3β Tyr216 phosphorylation. This highlights its potential as a therapeutic agent for cognitive impairment.