Aquilaria crassna Extract Exerts Neuroprotective Effect against Benzo[a]pyrene-Induced Toxicity in Human SH-SY5Y Cells: An RNA-Seq-Based Transcriptome Analysis

Benzo[a]pyrene (B[a]P) is known to inhibit neurodifferentiation and induce neurodegeneration. Agarwood or <i>Aquilaria crassna</i> (AC), a plant with health-promoting properties, may counteract the neurotoxic effects of B[a]P by promoting neuronal growth and survival. This study investigated the protective effect of AC leaf ethanolic extract (ACEE) on the B[a]P-induced impairment of neuronal differentiation. A transcriptomic analysis identified the canonical pathway, the biological network, and the differentially expressed genes (DEGs) that are changed in response to neuronal differentiation and neurogenesis. Several genes, including <i>CXCR4</i>, <i>ENPP2</i>, <i>GAP43</i>, <i>GFRA2</i>, <i>NELL2</i>, <i>NFASC</i>, <i>NSG2</i>, <i>NGB</i>, <i>BASP1</i>, and <i>NEUROD1</i>, in B[a]P-treated SH-SY5Y cells were up-regulated after treatment with ACEE. Notably, a Western blot analysis further confirmed that ACEE increased the protein levels of GAP43 and neuroglobin. B[a]P treatment led to decreased phosphorylation of Akt and increased phosphorylation of ERK in SH-SY5Y cells; however, ACEE was able to reverse these effects. Clionasterol and lupenone were identified in ACEE. Molecular docking showed that these two phytochemicals had significant interactions with CXCR4, GDNF family receptor alpha (GFRA), and retinoid X receptors (RXRs). In conclusion, ACEE may be a potential alternative medicine for the prevention of impaired neuronal differentiation and neurodegenerative diseases.