从 RNA-Seq 转录组分析探讨 Extract Exerts 对苯并[a]芘诱导的人 SH-SY5Y 细胞毒性的神经保护作用。

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

机构信息

Center of Excellence on Natural Products for Neuroprotection and Anti-Ageing (Neur-Age Natura), Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

Nutrients. 2024 Aug 16;16(16):2727. doi: 10.3390/nu16162727.

DOI:10.3390/nu16162727

PMID:39203863

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11357018/

Abstract

Benzo[a]pyrene (B[a]P) is known to inhibit neurodifferentiation and induce neurodegeneration. Agarwood or (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 , , , , , , , , , and , 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.

摘要

苯并[a]芘（B[a]P）已知能抑制神经分化并诱导神经退行性变。沉香或（AC），一种具有促进健康特性的植物，可能通过促进神经元生长和存活来抵消 B[a]P 的神经毒性作用。本研究调查了沉香叶乙醇提取物（ACEE）对 B[a]P 诱导的神经元分化损伤的保护作用。转录组分析确定了经典途径、生物网络以及响应神经元分化和神经发生而改变的差异表达基因（DEGs）。在 B[a]P 处理的 SH-SY5Y 细胞中，包括、、、、、、、、和在内的几个基因在 ACEE 处理后上调。值得注意的是，Western blot 分析进一步证实 ACEE 增加了 GAP43 和神经球蛋白的蛋白水平。B[a]P 处理导致 SH-SY5Y 细胞中 Akt 的磷酸化减少和 ERK 的磷酸化增加；然而，ACEE 能够逆转这些效应。在 ACEE 中鉴定出了 clionasterol 和 lupenone。分子对接表明，这两种植物化学物质与 CXCR4、GDNF 家族受体 alpha（GFRA）和视黄酸 X 受体（RXRs）具有显著的相互作用。总之，ACEE 可能是预防神经元分化受损和神经退行性疾病的潜在替代药物。