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

Nattaporn Pattarachotanant, Center of Excellence on Natural Products for Neuroprotection and Anti-Ageing (Neur-Age Natura), Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Suporn Sukjamnong, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Panthakarn Rangsinth, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Kamonwan Chaikhong, Center of Excellence on Natural Products for Neuroprotection and Anti-Ageing (Neur-Age Natura), Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Chanin Sillapachaiyaporn, Center of Excellence on Natural Products for Neuroprotection and Anti-Ageing (Neur-Age Natura), Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
George Pak-Heng Leung, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Valerie W. Hu, Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Tewarit Sarachana, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Siriporn Chuchawankul, Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Tewin Tencomnao, Center of Excellence on Natural Products for Neuroprotection and Anti-Ageing (Neur-Age Natura), Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Anchalee Prasansuklab, Center of Excellence on Natural Products for Neuroprotection and Anti-Ageing (Neur-Age Natura), Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

Document Type

Journal Article

Publication Date

8-16-2024

Journal

Nutrients

Volume

16

Issue

16

DOI

10.3390/nu16162727

Keywords

RNA sequencing; agarwood; molecular docking; neurite outgrowth; neurotoxicity; polycyclic aromatic hydrocarbons; signaling pathways

Abstract

Benzo[a]pyrene (B[a]P) is known to inhibit neurodifferentiation and induce neurodegeneration. Agarwood or Aquilaria crassna (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 CXCR4, ENPP2, GAP43, GFRA2, NELL2, NFASC, NSG2, NGB, BASP1, and NEUROD1, 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.

Department

Biochemistry and Molecular Medicine

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