ABSTRACT: Benzo[a]pyrene (B[a]P) has been recognized to inhibit neurodifferentiation and to be a cause of neurodegenerative diseases. Agarwood or Aquilaria crassna (AC), a useful plant for health-promoting properties, has the potential to counteract B[a]P by promoting neuronal growth and survival. In this study, the protective effect of AC leaf ethanolic extract (ACEE) on B[a]P-induced impaired neuronal differentiation was investigated. We employed transcriptomic analysis and identified the canonical pathway, the biological network, and differentially expressed genes (DEGs) that changed their expression levels consistently in response to neuronal differentiation and neurogenesis. Several genes, such as CXCR4, ENPP2, GAP43, GFRA2, NELL2, NFASC, NSG2, NGB, BASP1, and NEUROD1, mediated neuroprotective effect of ACEE in B[a]P-exposed SH-SY5Y cells. Notably, the biological network of these genes and Western blot confirmed that neuroglobin (NGB) was an important key in this study. Moreover, ACEE protected the neurons through the PI3K/Akt and ERK-signaling pathways. ACEE-identified phytochemicals, clionasterol and lupenone, were the possible constituents that acted as potent agonists for the CXCR4, GFRA, and RXR receptors. Therefore, ACEE could be a potential alternative medicine to prevent B[a]P-impaired neuronal differentiation and neurodegenerative diseases.
